BMJ

Confidential: For Review Only Harnessing genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomization study

Journal: BMJ

Manuscript ID BMJ-2019-052821.R1

Article Type: Research

BMJ Journal: BMJ

Date Submitted by the 31-Jan-2020 Author:

Complete List of Authors: Richardson, Tom; University of Bristol Faculty of Health Sciences, MRC Integrative Epidemiology Unit Sanderson, Eleanor; University of Bristol, Population Health Sciences Elsworth, Benjamin; University of Bristol, MRC Integrative Epidemiology Unit (IEU), Bristol Medical School: Population Health Science Tilling, Kate; University of Bristol Faculty of Health Sciences Davey Smith, George; MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine

Mendelian randomization, Mediation, Early life adiposity, UK Biobank, Keywords: ALSPAC

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1 2 3 4 Harnessing genetic variation to separate the effects of early and later life 5 6 adiposity on disease risk: mendelian randomization study 7 8 9 10 11 Tom G. Confidential:Richardson1,*, Eleanor Sanderson1 , ForBenjamin ReviewElsworth1, Kate Tilling Only1, George Davey Smith1 12 13 1MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of 14 15 Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom 16 17 18 19 *Corresponding author: Dr Tom G. Richardson, MRC Integrative Epidemiology Unit, Population 20 21 Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol 22 23 BS8 2BN, UK. Tel: +44 (0)117 3313370; E-mail: [email protected] 24 25 26 27 28 Word Count: 5,739 29 30 Key words: Mendelian randomization, Early life adiposity, Mediation, UK Biobank, 31 32 ALSPAC 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 2 of 192

1 2 3 4 5 Abstract 6 Objective: To evaluate whether early life body size has an independent effect on later life 7 8 disease risk or whether its influence is mediated by adulthood body size. 9 10 Design: Two-sample univariable and multivariable Mendelian randomization. 11 Confidential: For Review Only 12 Setting: The UK Biobank (UKB) prospective cohort study and four large-scale genome-wide 13 association study (GWAS) consortia. 14 15 Participants: 453,169 participants enrolled in the UKB and a combined total of over 16 17 700,000 individuals from different GWAS consortia. 18 19 Exposures: Measured body mass index during adulthood (mean age: 56.5) and self-reported 20 body size at age 10. 21 22 Main outcome measures: Coronary artery disease (CAD), type 2 diabetes (T2D), breast 23 24 cancer and prostate cancer. 25 26 Results: Individuals with a larger genetically predicted body size in early life had increased 27 odds of CAD (OR:1.49 per change in body size category unless stated otherwise, 95% CI:1.33- 28 29 1.68) and T2D (OR :2.32, 95% CI:1.76-3.05) based on univariable MR (UVMR) analyses. 30 31 However, there was little evidence of a direct effect (i.e. not via adult body size) based on 32 33 multivariable MR (MVMR) estimates (CAD OR:1.02, 95% CI:0.86-1.22, T2D OR:1.16, 95% 34 35 CI:0.74-1.82). In the MVMR analysis of breast cancer risk, there was strong evidence of a 36 protective direct effect for larger body size in early life (OR:0.59, 95% CI:0.50-0.71), with less 37 38 evidence of a direct effect of adult BMI on this outcome (OR:1.08, 95% CI:0.93-1.27). Adding 39 40 age of menarche as an additional exposure provided weak evidence of a total causal effect 41 42 (UVMR OR:0.98, 95% CI:0.91-1.06) but strong evidence of a direct causal effect, independent 43 of early life and adult body size (MVMR OR:0.90, 95% CI:0.85-0.95). There was no strong 44 45 evidence of a causal effect of either early or later life measures on prostate cancer (early life 46 47 body size OR:1.06, 95% CI:0.81-1.40, adult body size OR:0.87, 95% CI:0.70-1.08). 48 49 Conclusions: Our findings suggest that the association between childhood body size and 50 CAD and T2D risk can be attributed to the continuity of adiposity into later life. However, 51 52 having a lower BMI during childhood may increase risk of breast cancer regardless of body 53 54 size in adulthood, with timing of puberty also putatively playing an important role. 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 3 of 192 BMJ

1 2 3 4 5 Introduction 6 Childhood obesity is now widely recognised as a global public health crisis, yet its prevalence 7 8 continues to rise1 2. Having a high body mass index (BMI) in early life is thought to increase 9 10 the risk of various health conditions, such as coronary artery disease (CAD)3, type 2 diabetes 11 Confidential: For Review Only 4 5-7 12 (T2D) and different types of cancer . Whether an individual can reverse the impact of 13 childhood obesity through lifestyle modifications is unclear, particularly given that 14 15 individuals who are obese in early life tend to remain obese in adulthood8. This makes it 16 17 challenging to discern whether early life adiposity has an independent and lasting influence 18 19 on disease risk, or if its effect is entirely mediated by later life adiposity. If the latter is the 20 case, then the potential adverse consequences of childhood obesity could be avoided by 21 22 attaining and maintaining a healthy weight in adulthood. 23 24 25 9 26 Mendelian randomization (MR) is an approach that can help address such issues , including 27 through harnessing genetic variants as instrumental variables to infer causality amongst 28 29 correlated traits10 11. As an individual’s genotype is established at zygote formation then 30 31 genetic variation is robust to reverse causation, and confounding is considerably less evident 32 12 33 than in conventional observational studies . Furthermore, recent methods have been 34 35 developed to disentangle whether several exposures influence an outcome along the same 36 causal pathway or whether they have independent effects13 14. One of these developments is 37 38 known as multivariable Mendelian randomization13 15. 39 40 41 42 We have undertaken an MR study to evaluate whether genetically predicted early life body 43 size has an effect on 4 disease outcomes that have been linked to childhood adiposity: CAD, 44 45 T2D, breast cancer and prostate cancer3 4 7 16. Genetic instruments were identified by 46 47 undertaking a genome-wide association study (GWAS) of 453,169 individuals from the UK 48 49 Biobank study with measures of BMI in adulthood (mean age=56.5) who also reported their 50 body size at age 10. This allowed us to conduct both univariable and multivariable MR 51 52 analyses to discern whether the predicted causal influence of early life body size has an 53 54 independent effect on disease risk, or whether the effect is mediated through later life BMI. 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 4 of 192

1 2 3 We postulate that, if early life body size has a causal influence on disease risk, then there are 4 5 likely 3 main categories that such effects could be grouped into after accounting for body size 6 7 during adulthood in a multivariable framework (Figure 1). Firstly, the influence of early life 8 9 body size on disease risk may be mediated by later life body size. As such, early life body size 10 only has an indirect effect on disease risk via adult body size, which for example could be 11 Confidential: For Review Only 12 attributed to individuals with a high BMI at age 10 remaining overweight into adulthood 13 14 (Figure 1-1). Secondly, early life body size may have only an independent (i.e. direct) effect 15 16 on disease risk, which is not mediated through adult body size (Figure 1–2). Thirdly, body 17 size at separate timepoints may both influence disease risk via alternate causal pathways 18 19 (i.e. early life body size has both a direct and an indirect effect on outcome, Figure 1–3). These 20 21 scenarios are possible to investigate using multivariable MR given that it has been recently 22 23 demonstrated by GWAS that genetic variation may have varying effects on body size at 24 different stages in the life course17. Additional descriptions of direct, indirect and total effects 25 26 within a multivariable framework can be found in Supplementary Figure 1. 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 5 of 192 BMJ

1 2 3 4 5 Methods 6 7 The UK Biobank and disease outcome datasets 8 Between 2006 to 2010 the UK Biobank study enrolled 500,000 individuals aged between 40 9 10 and 69 at baseline across 22 assessments centres in the United Kingdom18. Data were 11 Confidential: For Review Only 12 collected based on clinical examinations, assays of biological samples, detailed information 13 19 14 regarding self-reported health characteristics and genome-wide genotyping . BMI was 15 derived using height (measured in whole centimetres) and weight (to the nearest 0.1kg) 16 17 measured at baseline. Participants were also asked ‘When you were 10 years old, compared 18 19 to average would you describe yourself as thinner, plumper or about average?’. Hereafter 20 21 this measure is referred to as ‘early life body size’. Only individuals with both early life and 22 adult measures were included in analyses. Adult BMI was converted into a categorical 23 24 variable with 3 groups based on the same proportions as the early life body size variable (i.e. 25 26 ‘thinner’, ‘plumper’ and ‘about average’). This was to ensure that both measures were as 27 28 comparable as possible. This measure is referred to as ‘adult body size’ hereafter. Effect 29 estimates from our results can be interpreted as the increase in odds conferred per additive 30 31 change in body size category. 32 33 34 35 In total, 12,370,749 genetic variants in up to 463,005 individuals were available for analysis 36 as described previously20. Effect estimates for genome-wide genetic variants on CAD21, 37 38 T2D22, breast cancer23 and prostate cancer24 were obtained using findings from large-scale 39 40 consortia which did not include data from the UK Biobank (Supplementary Table 1). Since 41 42 earlier age at menarche is an established risk factor for breast cancer we also obtained 43 summary statistics from a GWAS of age of menarche, which was used in additional analyses 44 45 relating to this outcome25. 46 47 48 49 The Avon Longitudinal Study of Parents and Children (ALSPAC) 50 51 ALSPAC is a population-based cohort study investigating genetic and environmental factors 52 that affect the health and development of children. The study methods are described in detail 53 54 elsewhere26 27. In brief, 14,541 pregnant women residents in the former region of Avon, UK, 55 56 with an expected delivery date between April 1, 1991 and December 31, 1992, were eligible 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 6 of 192

1 2 3 to take part in ALSPAC. Detailed phenotypic information, biological samples and genetic data 4 5 have been collected from the participants which are available through a searchable data 6 7 dictionary (http://www.bris.ac.uk/alspac/researchers/our-data/). Written informed 8 9 consent was obtained for all study participants. Ethical approval for the study was obtained 10 from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. 11 Confidential: For Review Only 12 Further details on genotyping and trait measurements in the ALSPAC cohort can be found in 13 14 Supplementary Note 1. 15 16 17 18 Statistical analysis 19 20 21 Identifying instruments by undertaking a genome-wide association study 22 23 The association between genetic variants across the human genome and both measures of 24 25 body size were assessed using the software BOLT-LMM20 28. This approach applies a 26 27 Bayesian linear mixed model to evaluate the association between each genetic variant with 28 each measure of body size in turn, whilst accounting for both relatedness and population 29 30 stratification. Age at baseline and type of genotyping array were added as covariates in the 31 32 model. Analyses were undertaken 3 times, once in all eligible individuals after additionally 33 34 adjusting for sex, and then in females and males separately. This allowed us to identify 35 genetic variants which could be used as instrumental variables for outcomes based on a 36 37 female-only population (i.e. breast cancer), a male-only population (i.e. prostate cancer) and 38 39 mixed populations (i.e. CAD and T2D). Early life body size analyses were additionally 40 41 adjusted for month of birth as we hypothesized that an individual’s relative age within their 42 43 school year may bias their reporting. Effect estimates from this analysis were used in the 44 subsequent Mendelian randomization analyses. We used linear regression, i.e. assuming that 45 46 the effect of a given SNP on moving from the lowest to the middle category of the body size 47 48 variables is the same as its effect on moving from the middle to the highest. 49 50 51 The genetic correlation between the early life and adult body size GWAS results was 52 53 calculated using bivariate GREML analysis using GCTA software29. A genetic relationship 54 55 matrix was derived from 10,000 randomly selected UK Biobank participants who were 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 7 of 192 BMJ

1 2 3 unrelated and of European descent. Linkage disequilibrium (LD) clumping was undertaken 4 5 using the software PLINK30 to identify independent variants from our GWAS. This was based 6 7 on a threshold of r2 <0.001 using genotype data from European individuals (CEU) from phase 8 31 9 3 (version 5) of the 1000 genomes project as a reference panel . For independent variants 10 associated with either early life or adult body size in our GWAS of all participants (based on 11 Confidential: For Review Only 12 P < 5 x 10-08), we compared their effect estimates between timepoints. This was undertaken 13 14 by stacking observations (i.e. so that each individual had 2 body size measurements) and 15 16 then regressing the categorical body size outcomes on each variant in turn adjusting for age, 17 sex and time (i.e. early life or adulthood). This analysis was then repeated but also adjusting 18 19 for the interaction between genetic variant and time. To account for multiple testing, we 20 21 applied a Bonferroni correction to the p-values of the interaction terms (i.e. P < 0.05/number 22 23 of individual variants assessed) as a heuristic to highlight genetic loci with the strongest 24 evidence of an interaction with time. This analysis was undertaken to demonstrate that 25 26 various genetic variants seemingly appear to have a stronger influence on body size at 27 28 different timepoints in the life courses. 29 30 31 32 Validation of genetic scores using external datasets 33 34 Data on clinically measured BMI from the Avon Longitudinal Study of Parents and Children 35 36 (ALSPAC) cohort was used to validate the scores we generated in the UK Biobank study. BMI 37 38 data was obtained at 3 timepoints; 2 based on the ALSPAC offspring (at mean ages 9.9 and 39 40 17.9 years) and 1 in the ALSPAC mothers (mean age 50.8 years). Measures of BMI were 41 dichotomised to classify individuals higher than the 85th percentiles as ‘overweight’. 42 43 Receiver operator characteristic (ROC) curves were generated using the ‘plotROC’ R package 44 45 to compare the predictive ability of both the early life and adult body size scores at all 3 46 47 timepoints. 48 49 50 We also undertook LD score regression32 to evaluate the genetic correlation between the two 51 52 measures of body size from our analysis with directly measured adult BMI33 and childhood 53 34 35 54 obesity using large-scale external populations based on data from LD hub . This was 55 undertaken to further validate our early life measure of body size by demonstrating that it is 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 8 of 192

1 2 3 more strongly correlated with measured child obesity than adult BMI. This was particularly 4 5 important to demonstrate given that the early life body size score in UK Biobank was derived 6 7 using questionnaire recall data which could lead to bias if not appropriately validated using 8 9 external datasets. 10 11 Confidential: For Review Only 12 Mendelian randomization 13 14 Univariable MR analyses were conducted using the MR-Base platform36 to investigate total 15 16 effect estimates between genetically predicted early life and adult body size individually with 17 18 each disease outcome in turn. This was based on the inverse-variance weighted (IVW) 19 method which estimates the causal effect of an exposure on an outcome by combining ratio 20 21 estimates using each variant in a fixed-effect meta-analysis model37. Effect estimates on early 22 23 life body size were used for the analysis with additional adjustment for month of birth. 24 25 However, the “total” effect of adult body size should be interpreted with caution. There is 26 likely to be strong correlation between genetic determinants of early and adult body size, 27 28 and thus the total effect of adult body size is likely to suffer from what will manifest as 29 30 pleiotropy if there is also a direct effect of early body size on the outcome. In the main 31 32 manuscript we only discuss the total effect of early body size, and direct effects of early and 33 adult body size, for this reason. A direct acyclic graph illustrating direct, indirect and total 34 35 effects as investigated within a multivariable MR framework can be found in Supplementary 36 37 Figure 1. 38 39 40 Multivariable MR analyses were undertaken to estimate the direct effect of early life body 41 42 size on each outcome in turn. Variants from the univariable analysis were used again here 43 44 after undertaking further LD clumping to account for instrument correlation between the 45 46 two sets. We also undertook a negative control analysis with early life and adult body size as 47 exposures in a multivariable framework and age at menarche as an outcome using findings 48 49 from a GWAS published prior to the release of UK Biobank25. As depicted in Supplementary 50 51 Figure 2, we hypothesized that early life body size should only influence age at menarche 52 53 directly in this framework as an individual’s adult body size cannot influence timing of 54 puberty. As such, direct and total effect derived from a univariable framework should be 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 9 of 192 BMJ

1 2 3 comparable for early life body size on this outcome, whereas evidence of an indirect effect 4 5 (i.e. via adult body size) should be weak. 6 7 8 9 Furthermore, we undertook a sensitivity analysis for the breast cancer outcome to discern 10 whether timing of puberty may also play a role in disease risk. This involved repeating 11 Confidential: For Review Only 12 analyses on breast cancer with age at menarche as a third exposure (along with early life and 13 14 adult BMI). Univariable and Multivariable MR analyses were also repeated using findings 15 16 derived from ER-positive and ER-negative cases of breast cancer. Moreover, we undertook 17 various sensitivity analyses to investigate results from the univariable and multivariable 18 19 analyses, such as assessing instrument strength by deriving F-statistics38, examining 20 21 heterogeneity using Cochran’s Q39 and investigating horizontal pleiotropy using the MR- 22 40 41 23 Egger method . Finally, we undertook a simulation study to investigate how 24 misclassification of early life body size could affect our results (Supplementary Note 2). 25 26 27 28 All analyses were undertaken using R (version 3.5.1). Plots were created using the packages 29 42 43 30 ‘ggplot2’ and ‘metafor’ . 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 10 of 192

1 2 3 4 5 Results 6 7 A genome-wide association study of early life and adult body mass index 8 In a GWAS of 453,169 UK Biobank individuals, there were 295 and 557 independent 9 10 associations detected with early life and adult body size respectively based on conventional 11 Confidential: For Review Only 12 genome-wide corrections (i.e. P < 5 x10-08) (Supplementary Tables 2 & 3). A genetic 13 14 correlation coefficient of rG=0.61 was calculated between these two sets of results. Using 15 individual-level data from the ALSPAC cohort, we found that a genetic score based on the 16 17 early life body size variants was a stronger predictor of childhood BMI (mean age 9.9 years) 18 19 compared to a score based on the adult variants (Figure 2A). Investigating the prediction of 20 21 both the early life and adult body size scores during later adolescence (mean age 17.8 years) 22 suggested that neither score was optimal at this timepoint (Figure 2B). During the adulthood 23 24 timepoint (mean age 50.8 years), the adult body size score was a better predictor than using 25 26 the early life body size variants (Figure 2C). These findings therefore demonstrate the ability 27 28 of these genetic instruments to separate early life and adult body size. 29 30 31 LD score regression analyses identified strong genetic correlation between our derived early 32 33 life measure of body size and a previous GWAS of childhood obesity (rg=0.85) 34 35 (Supplementary Figure 3). In contrast, our adult body size measure was considerably more 36 strongly genetically correlated with a previous GWAS of adult BMI (rg=0.96) than to 37 38 childhood obesity (rg=0.64). Evaluating the difference between the genetic variant 39 40 associations at the two different timepoints suggested that 75 genetic variants had stronger 41 42 effect estimates on body size in adulthood compared to early life, whereas 23 genetic 43 variants had a stronger effect in early life compared to adult body size estimates (at P < 7.19 44 45 x 10-05 (i.e. 0.05/694 tests), Supplementary Table 4). Demonstrating that the magnitude of 46 47 effect for these genetic variants differs with respect to early life and adult body size further 48 49 suggests that they can be separated as two exposures in a multivariable framework. Plotting 50 the relationship between early life body size and adult BMI in UK Biobank did not indicate 51 52 that there was a non-linear relationship between them in line with the assumptions of 53 54 multivariable MR (Supplementary Figure 4). Linear trajectories between childhood and 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 11 of 192 BMJ

1 2 3 adulthood have also been presented previously in cohorts such as the Fels Longitudinal 4 5 Study44. 6 7 8 9 Figure 3 illustrates findings from both GWAS using a bi-directional Manhattan plot 10 (sometimes referred to as a ‘Miami plot’) where some examples of timepoint specific effects 11 Confidential: For Review Only 12 have been highlighted. Repeating our GWAS stratified by sex identified 135 and 215 variants 13 14 which survived GWAS corrections (i.e. P < 5 x 10-08) in females only with early life and adult 15 16 body size respectively (n=246,511) (Supplementary Tables 5 & 6). In the male specific 17 analysis, there were 69 genetic variants associated with early life body size and 159 genetic 18 19 variants associated with adult body size (n=206,658) (Supplementary Tables 7 & 8). 20 21 Repeating early life body size analyses with additional adjustment for month of birth did not 22 23 appear to materially influence overall findings (Supplementary Table 9-11). 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 12 of 192

1 2 3 Univariable and multivariable Mendelian randomization analyses 4 5 Odds ratios from these analyses reflect the change in odds per change in category for our 6 7 derived early life and adult body size variables. Univariable analyses provided strong 8 9 evidence that early life body size is associated with CAD risk (UVMR OR:1.49, 95% CI:1.33- 10 11 1.68). However,Confidential: the direct effect of early For life body Review size (i.e. not mediated Only via adult body size) 12 was much smaller than the total effect (MVMR OR:1.02, 95% CI:0.86-1.22), whereas strong 13 14 evidence of a direct effect was identified for adult body size (OR:1.82, 95% CI:1.59-2.09). 15 16 Similar findings were identified for analyses of T2D, as the magnitude of the direct causal 17 18 effect for early life body size was much smaller than the total effect when modelled 19 simultaneously with the adult variable (early life body size OR:1.16, 95% CI:0.74-1.82, adult 20 21 body size OR:2.80, 95% CI:1.89-4.15). Effect estimates from both univariable and 22 23 multivariable MR analyses are illustrated in Figure 4 and a full list can also be found in 24 25 Supplementary Table 12. Furthermore, the results from this analysis were robust to the 26 various sensitivity analyses applied in this study (Supplementary Tables 13-15). 27 28 29 30 Evaluating the effect of early life body size on age at menarche as an outcome provided 31 32 strong evidence in the univariable analysis that having a larger body size at age 10 may result 33 in earlier timing of puberty (Beta:-0.93 standard deviation change in age at menarche per 34 35 change in body size category, 95% CI:-0.66 to -1.20). Including adult body size in the 36 37 multivariable framework, along with early life body size as an exposure, we found that the 38 39 direct effect estimate for early life body size was essentially unchanged (Table 1). In contrast, 40 there was weak evidence that adult body size has an effect on timing of puberty. These 41 42 findings reflect the scenario depicted in Supplementary Figure 2, suggesting that early life 43 44 body size can only effect timing of puberty directly and not indirectly via adult body size. 45 46 This analysis serves as a proof of concept for our multivariable framework, given that adult 47 body size cannot influence timing of puberty as it occurs at a later timepoint in the life course. 48 49 50 51 For breast cancer, there was strong evidence in the univariable analysis that higher 52 53 genetically predicted early life body size leads to reduced risk of this outcome (OR:0.63, 95% 54 CI:0.55-0.72). Analysing both measures of body size in a multivariable framework found that 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 13 of 192 BMJ

1 2 3 the indirect effect estimate via adult body size (OR:1.08, 95% CI:0.93-1.27) was smaller in 4 5 magnitude than the direct protective effect of early life body size (OR:0.59, 95% CI:0.50- 6 7 0.71). Similar findings were identified in the analysis of ER-positive and ER-negative cases 8 9 of breast cancer (Supplementary Table 16). 10 11 Confidential: For Review Only 12 Evaluating the relationship between genetically predicted age at menarche and breast 13 14 cancer in a univariable analysis provided weak evidence of a total effect (OR:0.98, 95% 15 16 CI:0.90-1.06). However, when modelled together with both early and adult body size (i.e. all 17 3 exposures in the multivariable model) there was strong evidence that later age at 18 19 menarche may lower the risk of breast cancer (OR:0.90, 95% CI:0.85-0.95). Effect estimates 20 21 for predicted early life body size had a larger effect in this multivariable analysis compared 22 23 to the direct effect of adult body size (Table 1). There was very weak evidence that early life 24 body size has a predicted causal effect on prostate cancer either directly (OR:1.06, 95% 25 26 CI:0.81-1.40). or indirectly via adult body size (OR:0.87, 95% CI:0.70-1.08). 27 28 29 30 Early life body size is self-reported later in life and so is likely to be subject to 31 misclassification, whereas adult body size is directly measured and is likely to be subject only 32 33 to random error. We therefore conducted a simulation to identify how such misclassification, 34 35 affecting only one exposure, could influence the effect estimation in our multivariable MR 36 37 analyses. Our simulation study (see Supplementary Note 2) shows that misclassification of 38 early life body size weakens the strength of association between the SNPs and our measure 39 40 of early life body size and so potentially biases the estimated effect of early life body size in 41 42 our multivariable MR analysis. These simulations do not cover all of the potential scenarios 43 44 for measurement error. However, in the scenarios we consider misclassification of early life 45 46 body size only introduces bias in the estimated effect of adult body size on the outcome when 47 the misclassification in early life body size is dependent on actual adult BMI and there is an 48 49 effect of early life body size on the outcome. The simulations also show that the direction of 50 51 this bias on the estimated effect of the adult variable will depend on the direction of effect of 52 53 the adult body size relative to the early life measure. Furthermore, the effect of adult body 54 size is unbiased when early life body size has no effect on the outcome. 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 14 of 192

1 2 3 Our simulation study also shows that the potential measurement error in self-reported age 4 5 10 body size has the potential to bias adult effects in our multivariable MR when the 6 7 measurement error is dependent on observed adult BMI and early life body size has a causal 8 9 effect on the outcome. This therefore has the potential to affect the results we obtain for adult 10 body size on breast cancer. These simulations show that the bias from misclassification 11 Confidential: For Review Only 12 depends on both the type of misclassification and the size and direction of the effects of both 13 14 exposures on the outcome. However, they suggest that this misclassification only masks the 15 16 adult effect when it acts in the same direction as the early life effect on the outcome. We 17 therefore do not believe that this measurement error is hiding a risk-increasing effect of 18 19 adult body size on breast cancer, although it is possible that it is masking a larger protective 20 21 effect. 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 15 of 192 BMJ

1 2 3 4 Univariable analysis Multivariable analysis 5 6 Outcome Exposure nSNPs Beta SE P Beta SE P 7 Age at menarche - Perry et al (2014) Early life body size 102 -0.93 0.14 1.42 x 10-10 -0.94 0.15 3.87 x 10-10 8 Confidential:Adult body size For142 Review- - Only- -0.03 0.14 0.82 9 10 Early life body size 124 -0.46 0.07 3.84 x 10-11 -0.64 0.10 1.57 x 10-10 11 Breast cancer - Michailidou et al (2017) Adult body size 191 - - - 0.06 0.09 0.52 12 Age at menarche 60 -0.02 0.04 0.58 -0.10 0.03 4.84 x 10-03 13 14 15 Table 1: Estimates from univariable and multivariable Mendelian randomization analysis assessing the effect of both 16 17 predicted early life and adult body size on age at menarche. We also conducted a sensitivity analysis to investigate how 18 19 both these exposures influence breast cancer risk when modelled with age at menarche as an additional third exposure. nSNPs 20 21 – number of variants used as instrumental variables, Beta – effect estimate coefficient per standardized unit change in exposure, 22 OR – odds ratio, SE – standard error of the estimate, P – corresponding p-value. 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 https://mc.manuscriptcentral.com/bmj 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 BMJ Page 16 of 192

1 2 3 4 5 Discussion 6 7 8 Interpretation of findings 9 10 In this study we have examined the influence of early life adiposity on disease risk and 11 Confidential: For Review Only 12 whether this putative causal effect occurs independently (“direct effect”) or via the same 13 14 causal pathway (“indirect effect”) as later life body size. Our univariable MR analysis 15 suggested that genetically predicted early life body size increases risk of coronary artery 16 17 disease and type 2 diabetes. However, when analysed together with adult body size in a 18 19 multivariable framework the direct effect estimates for early life body size were 20 21 considerably attenuated and fully compatible with, and close to, the null in comparison to 22 the estimates of the total effects, suggesting that early life adiposity influences on these 23 24 outcomes are mediated by later life body size (as portrayed in the ‘Indirect effect of early life 25 26 body size only’ diagram in Figure 1). These findings imply that observed associations 27 28 between early life obesity and increased coronary artery disease and type 2 diabetes risk are 29 likely attributed to individuals with a high body size during childhood remaining overweight 30 31 into later life. This suggests that a window of opportunity exists to mitigate the detrimental 32 33 impact of early life body size on risk of these disease outcomes45 46. These findings 34 35 corroborate those from previous studies suggesting that there is no persistent influence of 36 childhood obesity on risk of type 2 diabetes and cardiovascular disease, unless adiposity is 37 38 sustained47 48. Furthermore, these findings highlight the importance taking into account 39 40 adult body size in order to assess whether childhood adiposity has a direct or persistent 41 49 50 42 effect on disease risk over the life course . 43 44 45 Our results also provide strong evidence that early life body size has a protective effect on 46 47 breast cancer risk, as has been previously reported from both observational and MR studies 48 51-54 49 which have not previously taken into account adult BMI . This was identified both as a 50 total and direct effect using univariable and multivariable MR analyses respectively, 51 52 suggesting that the effect of early life body size may persist into later life regardless of any 53 54 interventions that influence BMI variation. Furthermore, reported protective effect 55 56 estimates from MR studies between later life body size and breast cancer risk may be 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 17 of 192 BMJ

1 2 3 attributed to effects from childhood. This is in contrast to observational estimates suggesting 4 5 that higher adult BMI increases breast cancer risk, which could be attributed to confounding 6 7 factors which Mendelian randomization analyses are more robust to54. We note however 8 9 that this effect requires further investigation in subpopulations of pre- and post-menopausal 10 breast cancer patients from large-scale GWAS. This is particularly crucial given 11 Confidential: For Review Only 12 observational evidence suggesting that higher BMI increases the risk of invasive breast 13 14 cancer in post-menopausal women55. 15 16 17 As an additional test of our multivariable framework, we undertook a negative control 18 19 analysis to investigate the effect of early life body size on age at menarche in both a 20 21 univariable and multivariable framework accounting for adult body size. We found that 22 23 estimates were consistent from both analyses for early life body size, whereas the effect 24 estimates for adult body size in the multivariable analyses had a much smaller magnitude of 25 26 effect in comparison. This provides a powerful proof of concept for our analytical framework, 27 28 given that body size can only influence timing of puberty in early life whereas adult body size 29 30 cannot as it occurs earlier in the life course. Moreover, they support findings from the 31 literature suggesting that higher BMI in childhood can lead to earlier timing of puberty56. 32 33 Evidence is particularly strong in females, where it has been postulated that this may be due 34 35 to an evolutionary mechanism rendering adequate fat storage to sustain both mother and 36 57 37 growing fetus . 38 39 40 We undertook an additional analysis to investigate timing of puberty with respect to the 41 42 putative protective effect of early life body size on breast cancer risk. To do this, we 43 44 incorporated age at menarche as an additional exposure in our multivariable MR analysis. 45 46 Our findings corroborate similar analyses undertaken using a multivariable framework, 47 which suggests that later age at menarche has a protective effect on breast cancer risk but 48 49 only when accounting for early life body size58. However, there is strong evidence from the 50 51 literature of a relationship between timing of puberty and later life BMI59 60. Notably, our 52 53 results build upon previous findings by modelling early life and adult body size as two 54 separate exposures, with the direct effect of early life body size providing strong evidence of 55 56 a protective effect when accounting for age at menarche. Similar observational findings have 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 18 of 192

1 2 3 been reported recently in premenopausal women after adjusting for age at menarche61. 4 5 Developing insight into the underlying biological mechanisms explaining this effect may 6 7 highlight potentially modifiable pathways. In terms of proposed explanations, the earlier 8 9 pubertal onset attributed to higher childhood adiposity has been postulated to result in 10 slower pubertal growth62. This may therefore protect against rapid pubertal growth during 11 Confidential: For Review Only 12 adolescence which has been linked to increased breast cancer risk63. Hormonal mechanisms 13 14 may also play a role, such as higher estrogen levels in early life produced by an increase in 15 61 16 adipose tissue . Estrogenic effects have been reported to induce early life breast 17 differentiation, as well as increase the expression of tumor suppressor genes64. 18 19 20 21 We were unable to support previous evidence of an effect between genetically predicted 22 65 66 23 body size and prostate cancer risk . This relationship is complex due to the effect of 24 obesity on various hormones in males, such as an inverse relationship with prostate specific 25 26 antigen67 and a positive relationship with estrogen concentrations68. This outcome is 27 28 therefore worth revisiting using forthcoming findings from large-scale GWAS of prostate 29 30 cancer when they become available, using this study’s analytical framework. A greater 31 number of genetic instruments in males only is also likely to improve power for future 32 33 endeavours. Evaluating the influence of pubertal development on this outcome would also 34 35 be a worthwhile undertaking69. 36 37 38 We used univariable Mendelian randomization to estimate total effects of early body size, 39 40 and multivariable Mendelian randomization to estimate direct effects of early and adult body 41 42 size. In theory, the univariable estimate of the effect of adult body size (the total effect) and 43 44 the multivariable estimate (the direct effect) should be equal. However, if some genetic 45 46 variants influence both early and adult body size (albeit with different effect sizes), and early 47 life body size has a direct effect on the outcome, then this will potentially generate pleiotropy 48 49 in the univariable estimate of adult body size. This can be seen in the univariable estimate of 50 51 the effect of adult body size on breast cancer, which is quite different to the multivariable 52 53 estimate, probably due to the direct effect of early body size on breast cancer. For CAD, where 54 there is no direct effect of early body size on the outcome, then the univariable and 55 56 multivariable effects of adult body size are the same. This demonstrates one of the issues 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 19 of 192 BMJ

1 2 3 with Mendelian randomization of time-varying exposures – the univariable analyses cannot 4 5 identify critical or sensitive periods of exposure, but only an effect of a difference in the 6 7 cumulative lifetime exposure70-72. Moreover, As outlined in all the diagrams depicted in 8 9 Figure 1, we assume that childhood body size has an effect on adulthood body size in all 10 scenarios. Therefore, individuals who (for example) lower their BMI between childhood and 11 Confidential: For Review Only 12 adulthood may effectively break this mediated causal chain and reduce their elevated risk of 13 14 diseases such as coronary heart disease or type 2 diabetes. 15 16 17 18 Strengths and limitations of this study 19 20 The key strengths of our investigation include the large number of individuals from the UK 21 22 Biobank study with measures of both early and later life adiposity (n=453,169). This sample 23 24 size is unprecedented in the field to date, although we note that a caveat to this is having to 25 26 rely on retrospective questionnaire-based data for the early life variable. As such there will 27 likely be additional measurement error in the early life variable, which could be differential 28 29 with respect to adult body size (i.e. larger adults may misremember their age 10 size 30 31 differently compared to those who are thinner). The statistical power in our GWAS therefore 32 33 comes at a cost, although despite this we were able to recapitulate evidence of association 34 between genetic variants and early life body size measurements in the literature73 74. 35 36 Furthermore, we were able to validate our scores using individual-level data from the 37 38 ALSPAC cohort, demonstrating that the early life score was a superior predictor of childhood 39 40 adiposity, whereas the adult score performed better in adults. Along with the large sample 41 size in UK Biobank, other benefits of this approach included the fact that we were able to 42 43 harmonise our early life and adult measures all within the same sample of individuals. This 44 45 was undertaken to reduce the likelihood of bias due to differing samples, for example 46 47 between two separate GWAS consortia involving differing populations. Moreover, 48 49 measurements of childhood BMI taken from current generations may not reflect those of 50 older populations which contributed to the outcome estimates in our analysis, whereas the 51 52 UK Biobank individuals and the outcome GWASs are from similar birth cohorts. 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 20 of 192

1 2 3 Harnessing large-scale summary statistics from GWAS using two-sample MR is another 4 5 strength of this study. This circumvents the necessity of having both our exposures and 6 7 outcomes measured in the same sample. Moreover, along with using genetic variants to 8 9 mitigate the influence of confounding and reverse causation, a multivariable MR framework 10 has enabled us to investigate the independent effect of early life body size, which is extremely 11 Confidential: For Review Only 12 challenging in an observational setting. This framework therefore presents a powerful 13 14 means to investigate many other questions in epidemiology. These could be related to the 15 16 effect the same exposure at different timepoints in the life course, as investigated in this 17 study of body size, or examining whether different risk factors influence disease risk 18 19 independently or along the same causal pathway. Particularly given the large-scale 20 21 summary-level data which current health data researchers are fortunate to have access to, 22 23 this presents an attractive opportunity to dissect the lifecourse structure of the causes of 24 disease using Mendelian randomization. 25 26 27 28 Our univariable analysis used all the SNPs associated with each exposure. Although there are 29 30 variations in the SNPs associated with each of early life and adult BMI there is also 31 considerable overlap in the SNPs associated with each timepoint. Our univariable MR 32 33 analyses therefore capture pleiotropic effects of the SNPs through the other time point as 34 35 well as, for childhood BMI, the effect mediated by adult body size. This is a limitation of our 36 37 univariable MR analyses but highlights the importance of the multivariable MR to 38 disentangle the direct effects of child and adult body size. 39 40 41 42 A limitation that should be taken into consideration when interpreting our results is that it 43 44 is possible that participants from the UK Biobank may have also contributed to the large- 45 46 scale GWAS the results of which were used in this study. Overlapping exposure and outcome 47 samples in a two-sample MR analysis may result in overfitting, although currently there is 48 49 no way to robustly discern whether this is the case unless anonymous identifiers between 50 51 the UK Biobank and GWAS consortium can be linked together75. Moreover, estimates used in 52 53 this study are based solely on body size and BMI data from the UK Biobank. These findings 54 should therefore be evaluated in future cohorts when sample sizes make this possible. This 55 56 is particularly important as it has been shown that UK Biobank participants are highly 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 21 of 192 BMJ

1 2 3 selected which can be problematic for instrumental variables analyses76 77. We note however 4 5 that severe selection bias which can result in reversed estimates is unlikely to be in an issue 6 7 in our analyses given that they are consistent with previous MR studies54 78 79. Lastly, we note 8 9 that capturing non-linear effects between body size at different points in the life courses and 10 disease outcomes is challenging in a two-sample setting80. Future methods development 11 Confidential: For Review Only 12 regarding this is therefore warranted. 13 14 15 16 Conclusions 17 18 19 Using multivariable Mendelian randomization, we have provided strong evidence suggesting 20 that early life adiposity has a causal influence on breast cancer risk that acts independently 21 22 of later life body mass index. Conversely, our results suggest that the positive association 23 24 between early life adiposity and both coronary artery disease and type 2 diabetes is likely 25 26 due to individuals with a high body mass index remaining overweight in later life. Our 27 approach therefore yields insight into the pathway between early life risk factors such as 28 29 body mass index and disease outcomes. Furthermore, it provides scope to differentiate 30 31 between effects where the conferred risk is and is not reversable by achieving and 32 33 maintaining a healthy body mass index in adulthood. 34 35 36 37 38 What is already known on this topic? 39 40 - Childhood obesity is known to have a detrimental impact on various health conditions 41 and disease risk in later life. 42 43 44 45 - Body mass index in early life has been associated with increased odds of coronary 46 47 artery disease and type 2 diabetes observationally, but whether this effect is 48 49 immutable or whether lifestyle modifications can help mitigate it is unclear. 50 51 52 - The influence of early life body mass index on risk of other diseases, such as breast 53 54 cancer and prostate cancer, has been previously reported but the causal relationships 55 56 underlying these observations are complex and require further evaluation. 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 22 of 192

1 2 3 4 5 What this study adds? 6 7 - The influence of genetically predicted early life body size on odds of coronary artery 8 9 disease and type 2 diabetes was predominantly mediated through later life adiposity. 10 This suggests that individuals can reduce the impact of any conferred risk by reducing 11 Confidential: For Review Only 12 their relative weight as they enter adolescence. 13 14 15 16 - Findings for body size at age 10 suggested that it had a protective effect on breast 17 cancer risk which is independent of later life adiposity, although timing of puberty 18 19 likely also plays a causal role in this relationship. 20 21 22 - Although in this study we have focused on cardiometabolic and cancer outcomes, the 23 24 analytical approach we have used has considerable potential to investigate how risk 25 26 factor trajectories across life influence a range of health outcomes. 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 23 of 192 BMJ

1 2 3 4 5 Funding 6 This work was supported by the Integrative Epidemiology Unit which receives funding from 7 8 the UK Medical Research Council and the University of Bristol (MC_UU_00011/1, 9 10 MC_UU_00011/2 and MC_UU_00011/3). T.G.R is a UKRI Innovation Research Fellow 11 Confidential: For Review Only 12 (MR/S003886/1). 13 14 15 Competing Interests 16 The authors declare no conflicts of interest. 17 18 19 Acknowledgements 20 21 We would like to thank the participants of the UK Biobank study and to the GWAS consortia 22 23 (CARDIoGRAMplusC4D, DIAGRAM, BCAC and PRACTICAL) who made their summary 24 25 statistics publicly available for the benefit of this study. G.D.S conducts research at the NIHR 26 27 Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and 28 the University of Bristol. The views expressed in this publication are those of the author(s) 29 30 and not necessarily those of the NHS, the National Institute for Health Research or the 31 32 Department of Health. UK Biobank data was analysed under application 15825. UK Biobank 33 34 has received ethical approval from the UK National Health Service’s National Research Ethics 35 Service (ref 11/ NW/0382). 36 37 38 39 We are extremely grateful to all the families who took part in this study, the midwives for 40 41 their help in recruiting them and the whole ALSPAC team, which includes interviewers, 42 computer and laboratory technicians, clerical workers, research scientists, volunteers, 43 44 managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant 45 46 ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. GWAS 47 48 data were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust 49 Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 50 51 23andMe. 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 24 of 192

1 2 3 4 5 Figure Legends 6 Figure 1: Directed acyclic graphs depicting three possible scenarios that could explain 7 8 a causal effect between early life body size and disease outcomes. 1) ‘Indirect effect of 9 10 early life body size only’ – early life body size indirectly influences disease risk only via adult 11 Confidential: For Review Only 12 body size 2) ‘Direct effect of early life body size only’ – early life body size has a direct effect 13 on disease risk independent of adult body size and 3) ‘Both indirect and direct effects of early 14 15 life body size’ –early life body size exerts both direct and indirect effects on disease risk. 16 17 18 19 Figure 2: Receiver operator characteristic curves to compare the predictive capability 20 of the early life and adult body size scores across 3 timepoints in the Avon 21 22 Longitudinal Study of Children and Parents (ALSPAC). A) mean age 9.9 years in the 23 24 ALSPSAC offspring, B) mean age 17.9 years in the ALSPAC offspring and C) mean age 50.8 25 26 years in the ALSPAC mothers. Body mass index in the ALSPAC cohort was dichotomised 27 based on the 85th percentile in all analyses. 28 29 30 31 Figure 3: A bi-directional Manhattan plot to illustrate genetic variants across the 32 33 genome associated with early life body size (above) and adult body size (below). Points 34 35 highlighted into yellow highlight effects that provided stronger evidence of association with 36 early life body size, whereas points highlighted in blue were more strongly associated with 37 38 adult body size. These genetic loci have been annotated based on the nearest protein coding 39 40 gene to the top associated variant. 41 42 43 44 Figure 4: A forest plot illustrating direct and indirect effect for genetically predicted 45 46 early life body size on four different disease outcomes (coronary artery disease, type 47 48 2 diabetes, breast cancer and prostate cancer). Effects from the univariable and 49 50 multivariable Mendelian randomization (MR) analyses are in blue and red respectively. 51 Estimates are displayed as odds ratios with 95% confidence intervals (CIs). 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 25 of 192 BMJ

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1 2 3 60. Lee JM, Kaciroti N, Appugliese D, et al. Body mass index and timing of pubertal initiation in 4 boys. Arch Pediatr Adolesc Med 2010;164(2):139-44. doi: 5 6 10.1001/archpediatrics.2009.258 [published Online First: 2010/02/04] 7 61. Premenopausal Breast Cancer Collaborative G, Schoemaker MJ, Nichols HB, et al. 8 Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in 9 Premenopausal Women. JAMA Oncol 2018;4(11):e181771. doi: 10 10.1001/jamaoncol.2018.1771Confidential: [published For Online Review First: 2018/06/23] Only 11 62. Marti-Henneberg C, Vizmanos B. The duration of puberty in girls is related to the timing of 12 its onset. J Pediatr 1997;131(4):618-21. doi: 10.1016/s0022-3476(97)70073-8 [published 13 14 Online First: 1997/12/05] 15 63. Berkey CS, Frazier AL, Gardner JD, et al. Adolescence and breast carcinoma risk. Cancer 16 1999;85(11):2400-9. doi: 10.1002/(sici)1097-0142(19990601)85:11<2400::aid- 17 cncr15>3.0.co;2-o [published Online First: 1999/06/05] 18 64. Hilakivi-Clarke L, Forsen T, Eriksson JG, et al. Tallness and overweight during childhood 19 have opposing effects on breast cancer risk. Br J Cancer 2001;85(11):1680-4. doi: 20 21 10.1054/bjoc.2001.2109 [published Online First: 2001/12/18] 22 65. Rodriguez C, Freedland SJ, Deka A, et al. Body mass index, weight change, and risk of prostate 23 cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers 24 Prev 2007;16(1):63-9. doi: 10.1158/1055-9965.EPI-06-0754 [published Online First: 25 2006/12/21] 26 66. Benn M, Tybjaerg-Hansen A, Davey Smith G, et al. High body mass index and cancer risk-a 27 Mendelian randomisation study. Eur J Epidemiol 2016;31(9):879-92. doi: 28 29 10.1007/s10654-016-0147-5 [published Online First: 2016/04/12] 30 67. Harrison S, Tilling K, Turner EL, et al. Investigating the prostate specific antigen, body mass 31 index and age relationship: is an age-BMI-adjusted PSA model clinically useful? Cancer 32 Causes Control 2016;27(12):1465-74. doi: 10.1007/s10552-016-0827-1 [published Online 33 First: 2016/11/11] 34 68. Giovannucci E, Rimm EB, Liu Y, et al. Body mass index and risk of prostate cancer in U.S. 35 health professionals. J Natl Cancer Inst 2003;95(16):1240-4. doi: 10.1093/jnci/djg009 36 37 [published Online First: 2003/08/21] 38 69. Bonilla C, Lewis SJ, Martin RM, et al. Pubertal development and prostate cancer risk: 39 Mendelian randomization study in a population-based cohort. BMC Med 2016;14:66. doi: 40 10.1186/s12916-016-0602-x [published Online First: 2016/04/06] 41 70. Labrecque JA, Swanson SA. Interpretation and Potential Biases of Mendelian Randomization 42 Estimates With Time-Varying Exposures. Am J Epidemiol 2019;188(1):231-38. doi: 43 44 10.1093/aje/kwy204 [published Online First: 2018/09/22] 45 71. Holmes MV, Ala-Korpela M, Davey Smith G. Mendelian randomization in cardiometabolic 46 disease: challenges in evaluating causality. Nat Rev Cardiol 2017;14(10):577-90. doi: 47 10.1038/nrcardio.2017.78 [published Online First: 2017/06/02] 48 72. Labrecque JA, Swanson SA. Mendelian randomization with multiple exposures: the 49 importance of thinking about time. Int J Epidemiol 2019 doi: 10.1093/ije/dyz234 50 [published Online First: 2019/12/05] 51 52 73. Warrington NM, Howe LD, Paternoster L, et al. A genome-wide association study of body 53 mass index across early life and childhood. Int J Epidemiol 2015;44(2):700-12. doi: 54 10.1093/ije/dyv077 [published Online First: 2015/05/09] 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 30 of 192

1 2 3 74. Felix JF, Bradfield JP, Monnereau C, et al. Genome-wide association analysis identifies three 4 new susceptibility loci for childhood body mass index. Hum Mol Genet 2016;25(2):389- 5 6 403. doi: 10.1093/hmg/ddv472 [published Online First: 2015/11/26] 7 75. Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample 8 Mendelian randomization. Genet Epidemiol 2016;40(7):597-608. doi: 10.1002/gepi.21998 9 [published Online First: 2016/10/19] 10 76. Fry Confidential:A, Littlejohns TJ, Sudlow C, et al. For Comparison Review of Sociodemographic Only and Health-Related 11 Characteristics of UK Biobank Participants With Those of the General Population. Am J 12 Epidemiol 2017;186(9):1026-34. doi: 10.1093/aje/kwx246 [published Online First: 13 14 2017/06/24] 15 77. Hughes RA, Davies NM, Davey Smith G, et al. Selection bias in instrumental variable 16 analyses. 2018:192237. doi: 10.1101/192237 %J bioRxiv 17 78. Nordestgaard BG, Palmer TM, Benn M, et al. The effect of elevated body mass index on 18 ischemic heart disease risk: causal estimates from a Mendelian randomisation approach. 19 PLoS Med 2012;9(5):e1001212. doi: 10.1371/journal.pmed.1001212 [published Online 20 21 First: 2012/05/09] 22 79. Censin JC, Peters SAE, Bovijn J, et al. Causal relationships between obesity and the leading 23 causes of death in women and men. PLoS Genet 2019;15(10):e1008405. doi: 24 10.1371/journal.pgen.1008405 [published Online First: 2019/10/28] 25 80. Staley JR, Burgess S. Semiparametric methods for estimation of a nonlinear exposure-outcome 26 relationship using instrumental variables with application to Mendelian randomization. 27 Genet Epidemiol 2017;41(4):341-52. doi: 10.1002/gepi.22041 [published Online First: 28 29 2017/03/21] 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 31 of 192 BMJ

1 2 3 4 Supplementary material 5 Supplementary Figure 1: A direct acyclic graph to demonstrate direct, indirect and total 6 7 effects estimated within a multivariable Mendelian randomization framework 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 In a multivariable Mendelian randomization framework, the direct effect of exposure 1 on the

36 outcome can be estimated as 1, whilst its indirect effect is estimated as 2. The total effect is therefore 37 calculated as 1 + 2. 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 Supplementary Figure 2: An applied negative control example using age at menarche as 4 5 an outcome 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 A direct acyclic graph illustrating a multivariable Mendelian randomization (MVMR) analysis to 33 investigate the direct and indirect effect of early life body size on age at menarche. This analysis was 34 undertaken as a negative control, given that early life body size can only influence timing of puberty 35 directly as the indirect path via adult body size is not biologically plausible given that this outcome 36 occurs at an earlier stage in the life course. As such, the direct effect of early life body size as 37 calculated in the MVMR analysis should be the same as the total effect as derived by univariable 38 estimates. 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 Supplementary Figure 3: Genetic correlation analysis 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Using linkage disequilibrium (LD) score regression, we compared the genetic correlation between 17 18 our two exposures (early life and adult body body size) with measured adult body mass index 19 (BMI) and childhood obesity from two consortia (GIANT and EGG). 20 21 22 Supplementary Figure 4: Boxplots for early life and adult body size in UK Biobank 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 Early life body size is categorised into three groups in the UK Biobank study (based on whether 48 individuals considered themselves to be ‘thinner’, ‘about average’ or ‘plumper’. Adult body mass 49 index was measured as a continuous variable and normalised to have a mean=1 and standard 50 deviation=0. The categorical measurement for early life BMI made it challenging to investigate the 51 52 assumption regarding linearity between these exposures in our model. However, these boxplots do 53 not indicate that there was evidence against a linear relationship as there was an overall 54 incremental trend across categories. 55 56 57 58 59 60

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1 2 3 Supplementary Note 1: The Avon Longitudinal Study of Parents and Children (ALSPAC) 4 5 cohort description 6 7 All children were genotyped using the Illumina HumanHap550 quad genome-wide SNP 8 genotyping platform. ALSPAC mothers were genotyped using the Illumina human660W- 9 quad array at Centre National de 331 Génotypage (CNG). Genotypes were called with 10 Illumina GenomeStudio. Samples were removed if individuals were related or of non- 11 European genetic ancestry. Genetic variants were removed if they had >5% missingness 12 or a HardyConfidential: Weinberg equilibrium (HWE) For P-value Review <1.0x10-06. Imputation Only was performed 13 14 using Impute V2.2.2 against a reference panel from the Haplotype Reference Consortium 15 (HRCr1.1, 2016) based on approximately 31,000 phased whole genomes. The HRC panel 16 was phased using ShapeIt v2, and the imputation was performed using the Michigan 17 imputation server. After imputation, we filtered out variants and kept those with an 18 imputation quality score of ≥ 0.8 and minor allele frequency (MAF) > 0.01. 19 20 21 22 All BMI measurements were obtained at ALSPAC clinics. Height was measured to the 23 nearest 0.1 cm with a Harpenden Stadiometer (Holtain Crosswell), and weight was 24 measured to the nearest 0.1 kg on Tanita electronic scales. Body mass index (BMI) was 25 calculated as (weight [kg]/(height [m]2). 26 27 28 29 Supplementary Note 2: Simulation for child and adult BMI estimates 30 31 Our measure of early life body size is based on recalled relative body size at age 10, 32 reported by individuals much later in life. This measure is therefore likely to be subject 33 34 to misclassification due to individuals misremembering their relative body size. Such 35 recall bias will not affect our measure of later life adiposity which is constructed from 36 measures of height and weight taken at the UK Biobank clinic. We therefore computed a 37 simple simulation study to identify what likely effect such misclassification, affecting only 38 39 one exposure in a two-exposure model, will have on the estimated effects in our 40 multivariable MR estimation. 41 42 We set up our model with two positively correlated exposures which each have a causal 43 effect on an outcome. Each exposure is modelled to have a true continuous effect on the 44 outcome but is only observed to take one of three categories (0/1/2) to reflect the setup 45 46 of our body size data. For each exposure a set of 150 SNPs are available which predict the 47 exposures. The model is estimated using a two-sample multivariable MR estimation 48 where the SNP exposure associations are estimated in the same sample for both 49 50 exposures and the SNP outcome association is estimated in a separate sample. 51 Within this model we investigated five misclassification scenarios; (1) no 52 53 misclassification in either exposure, (2) random misclassification of 15% of the data in 54 exposure 1 (the equivalent of early life body size), (3) random misclassification of 30% 55 of the data in exposure 1, (4) misclassification of 30% of the data in exposure 1 to the 56 57 level observed for exposure 2 (the equivalent of adult body size) and (5) misclassification 58 of 30% of the data in exposure 1 to one category lower than the true value. Setting 4 59 represents a scenario where individuals misremember their childhood BMI as being the 60 same (relative to others) as their current body size and setting 5 represents a

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1 2 3 misclassification where respondents remember their childhood body size as being lower 4 5 than it was. In each case we considered three scenarios; where only exposure 2 has an 6 effect on the outcome, where exposures 1 and 2 both have positive effects on the outcome 7 and where exposure1 has a negative effect on the outcome and exposure 2 has a positive 8 effect on the outcome. In all cases exposure 2 is also more strongly predicted by the set 9 10 of SNPs than exposure 1. 11 12 As the trueConfidential: effect of each exposure onFor the outcomeReview is the effect Only of a change in the 13 continuous variable underlying the observed categorical exposure we have calculated the 14 effect on the outcome we expect to observe in the data as the effect of moving from the 15 mean of one category to the mean of the next1. 16 17 The results from the simulations are given in Supplementary Table 1. These results show 18 19 that there is some bias in the estimated effects, due to the classification of the exposure 20 into categories. This bias moves the estimated effect of both exposures away from the 21 null. Random misclassification in 푋1 or reclassification of 푋1 to a lower category group 22 weakens the strength of the instruments for and increases the bias in the estimated 23 푋1 24 effect of X1, but does not affect the estimate for 푋2 . However, the estimated effect of 푋2 is 25 decreased when observations for 푋1 are reclassified to the level observed for 푋2 and there 26 27 is a true causal effect of the 푋1 on the outcome that is in the same direction as for 푋2 . When 28 푋1 and 푋2 have effects that act in opposite directions then each effect is biased away from 29 the null. These results indicate that there is some potential for bias in the multivariable 30 31 MR estimation when there is a true causal effect of 푋1 on the outcome and 32 misclassification in 푋1 is dependent on 푋2 , however it is not possible to determine which 33 direction such a bias would act in. The direction of the bias will depend on the association 34 35 of each exposure with the outcome. 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 With Misclassification 4 5 No Misclassification 6 15% Random 30% Random 30% X2 Dependent 30% X1 Dependent 7 8 0 Confidential:0.49 -0.49 0 0.49 -0.49 For0 Review0.49 -0.49 0 Only0.49 -0.49 0 0.49 -0.49 9 10 11 -0.01 0.56 -0.58 -0.01 0.65 -0.67 -0.01 0.76 -0.79 -0.01 0.79 -0.81 -0.01 0.65 -0.67 12 13 Std. error 0.03 0.04 0.03 0.03 0.04 0.03 0.04 0.05 0.04 0.04 0.05 0.04 0.03 0.04 0.03 14 F – statistic 21.29 21.26 21.26 14.9 14.9 14.90 9.98 9.97 9.97 13.86 13.86 13.86 14.92 14.92 14.92 15 16 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 17 18 19 0.60 0.59 0.61 0.6 0.59 0.61 0.6 0.59 0.61 0.60 0.36 0.85 0.60 0.59 0.61 20 21 Std. error 0.03 0.03 0.02 0.03 0.03 0.02 0.03 0.03 0.25 0.03 0.03 0.03 0.03 0.03 0.02 22 F – statistic 28.29 28.31 28.31 28.29 28.29 28.29 28.23 28.27 28.26 30.79 30.79 30.79 28.3 28.3 28.3 23 24 25 N = 50,000. 2000 repetitions. Random misclassification is introduced by randomly re-allocating 15% or 30% of the observations for 푋1 to a category (0/1/2), with 5 or 10 % allocated to each 26 category respectively. X2 Dependent misclassification is introduced by re-allocating 30% of observations for 푋1 to their observed category for 푋2 . X1 dependent misclassification is introduced 27 by re-allocating 30% of the observations to the category lower (with observations in the lowest category left unchanged). 28 29 30 1. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 31 1992;135(11):1301-9. doi: 10.1093/oxfordjournals.aje.a116237 [published Online First: 1992/06/01] 32 33 34 35 36 37 38 39 40 41 42 43 https://mc.manuscriptcentral.com/bmj 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Page 37 of 192 BMJ

1 2 Index 3 Supplementary Table 1: Genome-wide association study consortia from which disease outcome effect estimates were obtained in this study 4 Supplementary Table 2: Genome-wide association study results for early life body size in the UK Biobank 5 6 Supplementary Table 3: Genome-wide association study results for adulthood body size in the UK Biobank 7 Supplementary Table 4: Comparison of genome-wide effect estimates between early life and adult body size in the UK Biobank 8 Supplementary Table 5: Genome-wide association study results for early life body size in the UK Biobank (Females only) 9 Supplementary Table 6: Genome-wide association study results for adulthood body size in the UK Biobank (Females only) 10 Supplementary Table 7: Genome-wide association study results for early life body size in the UK Biobank (Males only) 11 12 SupplementaryConfidential: Table 8: Genome-wide association For study resultsReview for adulthood Onlysize in the UK Biobank (Males only) 13 Supplementary Table 9: Genome-wide association study results for early life body size in the UK Biobank (with additional adjustment for month of birth) 14 Supplementary Table 10: Genome-wide association study results for early life body size in the UK Biobank (Females only with additional adjustment for month of birth) 15 Supplementary Table 11: Genome-wide association study results for early life body size in the UK Biobank (Males only with additional adjustment for month of birth) 16 Supplementary Table 12: Genetically determined effect estimates from univariable and multivariable Mendelian randomization analysis assessing the effect of both predicted early life and adult body size on 4 disease outcomes 17 18 Supplementary Table 13: F-statistics for univariable and multivariable Mendelian randomization analyses 19 Supplementary Table 14: Assessment of heterogeneity for all outcomes 20 Supplementary Table 15: Sensitivity analyses using multivariable MR Egger analysis to assess the effect of both predicted early life and adult body size on 4 disease outcomes 21 Supplementary Table 16: Univariable and multivariable Mendelian randomization analysis assessing the effect of both predicted early life and adult measures on breast cancer (ER+/ER- cases) 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 1: Genome-wide association study consortia from which disease outcome effect3 estimates were obtained in this study 4 5 6 Supplementary Table 4: Comparison of genome-wide effect estimates between early life and adult body7 size in the UK Biobank Supplementary Table 5: Genome-wide association study results for early life body size in the UK Biobank8 (Females only) Supplementary Table 6: Genome-wide association study results for adulthood body size in the UK Biobank9 (Females only) 10 Supplementary Table 7: Genome-wide association study results for early life body size in the UK Biobank (Males only) 11 Supplementary Table 8: Genome-wide association study results for adulthood size in the UK Biobank12 (Males only) Confidential: For Review Only Supplementary Table 9: Genome-wide association study results for early life body size in the UK Biobank13 (with additional adjustment for month of birth) Supplementary Table 10: Genome-wide association study results for early life body size in the UK Biobank14 (Females only with additional adjustment for month of birth) Supplementary Table 11: Genome-wide association study results for early life body size in the UK Biobank15 (Males only with additional adjustment for month of birth) 16 Supplementary Table 12: Genetically determined effect estimates from univariable and multivariable Mendelian randomization analysis assessing the effect of both predicted early life and adult body size on 4 disease outcomes 17 18 19 Supplementary Table 15: Sensitivity analyses using multivariable MR Egger analysis to assess the effect20 of both predicted early life and adult body size on 4 disease outcomes Supplementary Table 16: Univariable and multivariable Mendelian randomization analysis assessing21 the effect of both predicted early life and adult measures on breast cancer (ER+/ER- cases) 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 Supplementary Table 12: Genetically determined effect estimates from univariable and multivariable Mendelian randomization analysis assessing the effect of both predicted early life and adult body size on 4 disease outcomes 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 1: Genome-wide association study consortia from which disease outcome effect estimates were obtained in this study 3 4 5 Disease outcome Lead author name Consortium Pubmed ID 6 Coronary Artery Disease Nikpay CARDIoGRAMplusC4D 26343387 7 Type 2 Diabetes Morris DIAGRAM 22885922 8 Breast cancer Michailidou BCAC 29059683 9 Prostate cancer Schumacher PRACTICAL 29892016 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 1: Genome-wide association study consortia 2from which disease outcome effect estimates were obtained in this study 3 4 5 Year Sample size Number of cases Number of controls 6 2015 184,305 60,801 123,504 7 2012 69,033 12,171 56,862 8 2017 228,951 122,977 105,974 9 2018 140,254 79,148 61,106 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 Population 6 Mixed population (Males and females) 7 European (Males and females) 8 European (Females only) 9 European (Males only) 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 2: Genome-wide association study results for early life body size in the UK Biobank 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs1421085 16 53800954 FTO T C 8 rs543874 1 177889480 SEC16B A G 9 rs10182458 2 25150641 ADCY3 A G 10 rs62106258 2 417167 FAM150B T C 11 12 rs12992672 Confidential:2 632592 ForTMEM18 ReviewG OnlyA 13 rs7132908 12 50263148 FAIM2 G A 14 rs663129 18 57838401 MC4R G A 15 rs12042908 1 74997762 TNNI3K A G 16 rs12641981 4 45179883 GNPDA2 C T 17 18 rs55880046 16 19941557 GPRC5B T G 19 rs115319174 2 207066474 GPR1 G C 20 rs3798519 6 50788778 TFAP2B A C 21 rs11209943 1 72750500 NEGR1 A G 22 23 rs8030456 15 68076856 MAP2K5 C T 24 rs35918296 8 76862208 HNF4G C T 25 rs2238435 16 4014282 ADCY9 C G 26 rs7550711 1 110082886 GPR61 C T 27 rs4744246 9 96254464 FAM120A A G 28 29 rs34260097 6 100727703 SIM1 T G 30 rs12798028 11 47604639 NDUFS3 C T 31 rs56133711 11 27723334 BDNF G A 32 rs12110721 6 55190480 GFRAL G A 33 rs3810291 19 47569003 ZC3H4 G A 34 35 rs12429545 13 54102206 OLFM4 G A 36 rs1933437 13 28624294 FLT3 G A 37 rs113728099 18 58157767 MC4R G A 38 rs7377083 4 102708997 BANK1 C A 39 rs9265968 6 31315663 HLA-B A T 40 41 rs62037365 16 28868962 SH2B1 C G 42 rs7239114 18 45921214 ZBTB7C G A 43 rs7719067 5 153538241 MFAP3 A G 44 rs1775255 6 51243035 PKHD1 G T 45 rs75001243 7 93216002 GNGT1 C T 46 47 rs9260164 6 29911684 HLA-A C T 48 rs61978655 14 30491807 PRKD1 G A 49 rs16996644 20 15813475 MACROD2 C G 50 rs7084503 10 2666859 PFKP T C 51 rs4688359 3 61198880 FHIT C T 52 53 rs9291816 5 63932508 RGS7BP C T 54 rs12140153 1 62579891 INADL G T 55 rs7355953 3 85792137 CADM2 T C 56 rs7958241 12 49509262 LMBR1L A G 57 rs35162296 6 26318262 HIST1H4H C T 58 59 rs2767486 1 65991203 LEPR A G 60 rs41310284 10 102447647 PAX2 C A rs1384660 2 142299735 LRP1B G A

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1 2 rs3131336 6 28831611 TRIM27 C T 3 rs34196306 6 27425644 ZNF184 G C 4 rs3129942 6 32338283 C6orf10 G T 5 rs2303384 11 65640204 EFEMP2 C T 6 7 rs9603697 13 40783323 AL133318.1 C T 8 rs200744777 20 6609610 BMP2 T G 9 rs13254613 8 64804804 YTHDF3 A C 10 rs6001872 22 40703245 TNRC6B A G 11 rs13047416 21 40309436 ETS2 C G 12 Confidential: For Review Only 13 rs796915 6 154304628 OPRM1 C G 14 rs2594994 3 11339960 ATG7 T A 15 rs55726687 12 991306 WNK1 G A 16 rs1333010 13 66205228 PCDH9 G A 17 rs4432271 16 20245283 GP2 C T 18 19 rs78444298 1 184672098 EDEM3 G A 20 rs9538146 13 59199461 PCDH17 A G 21 rs117903946 16 67449639 ZDHHC1 G A 22 rs1576655 13 79587841 RBM26 A C 23 rs59714050 3 141267294 RASA2 T A 24 25 rs11215403 11 115058585 CADM1 G A 26 rs7656673 4 30840331 PCDH7 A G 27 rs72819571 17 2170501 SMG6 G T 28 rs11150745 17 78757626 RPTOR A G 29 rs2207894 20 54387343 CBLN4 C T 30 31 rs11642090 16 81730582 CMIP T C 32 rs788858 4 82138300 PRKG2 A G 33 rs818898 9 6970806 KDM4C A G 34 rs72755233 15 100692953 ADAMTS17 G A 35 rs2409743 8 11070360 XKR6 C G 36 37 rs12713889 2 77225361 LRRTM4 T C 38 rs2722406 7 24306762 NPY C T 39 rs2735556 3 88105360 CGGBP1 T C 40 rs13256357 8 9979535 MSRA C T 41 rs10796828 11 69490346 ORAOV1 T G 42 43 rs2187642 12 11855624 ETV6 A C 44 rs12606230 18 52492252 RAB27B T C 45 rs6449532 5 60715446 ZSWIM6 C T 46 rs10896348 11 68357368 PPP6R3 T C 47 rs1013737 18 937050 ADCYAP1 G C 48 49 rs17399739 10 87490850 GRID1 A G 50 rs17637472 17 47461433 RP11-81K2.1 G A 51 rs71231793 7 76682610 UPK3B T C 52 rs1199333 3 138091701 MRAS G T 53 rs2034963 3 48170802 CDC25A G C 54 55 rs39862 5 66185151 MAST4 T C 56 rs11777719 8 8581038 CLDN23 A G 57 rs1865719 14 79923667 NRXN3 A G 58 rs1342831 6 54096151 MLIP T C 59 rs7989098 13 27925496 GTF3A T C 60 rs11525873 7 138817193 TTC26 T C

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1 2 rs117911387 9 130446836 STXBP1 G A 3 rs2229330 1 6649228 ZBTB48 T G 4 rs9438393 1 205782718 SLC41A1 A G 5 rs200801362 6 31555480 LST1 T C 6 7 rs7161424 14 33309274 AKAP6 G A 8 rs116399833 19 18502374 LRRC25 C A 9 rs754635 3 42305131 CCK C G 10 rs1935354 9 27822531 LINGO2 T C 11 rs2275241 9 129370576 LMX1B G A 12 Confidential: For Review Only 13 rs12214497 6 10015908 OFCC1 G T 14 rs7306710 12 66376091 HMGA2 T C 15 rs77960 5 103964585 NUDT12 G A 16 rs78607331 12 57648644 R3HDM2 C T 17 rs4889630 16 30877544 BCL7C T C 18 19 rs630602 1 54728864 SSBP3 G C 20 rs7606059 2 188152749 CALCRL T C 21 rs7305424 12 118399491 KSR2 A T 22 rs61937656 12 39483502 CPNE8 G A 23 rs73422097 6 41727740 PGC A G 24 25 rs957512 9 120405705 TLR4 T C 26 rs1452991 6 141473363 NMBR G A 27 rs7619139 3 25110415 RARB T A 28 rs355748 3 153964496 ARHGEF26 G T 29 rs10790809 11 126372550 KIRREL3 A G 30 31 rs7012648 8 28091482 ELP3 G A 32 rs947088 20 17171373 PCSK2 G T 33 rs2968973 4 130740404 C4orf33 C T 34 rs3817428 15 89415247 ACAN C G 35 rs836179 12 50503082 GPD1 A G 36 37 rs7625768 3 131774642 CPNE4 G A 38 rs62425398 6 166416028 PDE10A C A 39 rs11205303 1 149906413 MTMR11 T C 40 rs601338 19 49206674 FUT2 G A 41 rs6979832 7 127856276 LEP A G 42 43 rs112898427 2 67561335 ETAA1 C T 44 rs661878 11 29188691 METTL15 A G 45 rs1800437 19 46181392 GIPR G C 46 rs7808296 7 103127620 RELN C T 47 rs146910503 2 25446473 DNMT3A G A 48 49 rs7759938 6 105378954 LIN28B C T 50 rs7237444 18 39468982 PIK3C3 G A 51 rs824207 15 24007729 NDN A G 52 rs1422067 5 77424836 AP3B1 C T 53 rs7162542 15 84514290 ADAMTSL3 C G 54 55 rs2970356 15 90623540 ZNF710 C G 56 rs4074404 1 187683956 PLA2G4A T A 57 rs12045879 1 15817090 CELA2B C T 58 rs1808579 18 21104888 NPC1 C T 59 rs9299 17 46669430 HOXB3 C T 60 rs9366803 6 32621132 HLA-DQB1 T C

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1 2 rs7020564 9 109670016 ZNF462 A T 3 rs28629903 12 122497001 BCL7A T C 4 rs10095724 8 53739232 RB1CC1 G A 5 rs8048855 16 24830839 TNRC6A G T 6 7 rs7536458 1 118864602 SPAG17 T G 8 rs34517439 1 78450517 DNAJB4 C A 9 rs8096658 18 77156537 NFATC1 C G 10 rs4958568 5 152016093 NMUR2 G A 11 rs7424771 2 161276378 RBMS1 G A 12 Confidential: For Review Only 13 rs4572029 10 70889053 VPS26A A G 14 rs2246623 17 74084449 EXOC7 C T 15 rs918472 5 170738836 TLX3 G A 16 rs2141004 2 6194359 DKFZP761K2322 A C 17 rs10133279 14 82702712 SEL1L C T 18 19 rs35588936 1 155950963 ARHGEF2 C T 20 rs9922288 16 24550930 RBBP6 A G 21 rs77976727 8 4300554 CSMD1 C T 22 rs2629881 3 59778271 FHIT C T 23 rs78907487 22 22151939 MAPK1 A C 24 25 rs35926495 3 50255663 GNAI2 C T 26 rs4985555 16 70690166 IL34 A G 27 rs10503246 8 4130363 CSMD1 A G 28 rs262338 7 103417134 RELN G T 29 rs435775 6 97237609 GPR63 A G 30 31 rs7753558 6 117523471 VGLL2 C A 32 rs7951870 11 46373311 DGKZ T C 33 rs6783281 3 84791851 CADM2 A G 34 rs35189091 4 137147696 PCDH18 A G 35 rs1552759 12 99640557 ANKS1B T C 36 37 rs34811474 4 25408838 ANAPC4 G A 38 rs2356864 1 50839740 DMRTA2 G A 39 rs3810304 19 30861683 ZNF536 A G 40 rs7522014 1 66551759 PDE4B A G 41 rs2115885 5 87598818 TMEM161B G A 42 43 rs212517 1 21577159 ECE1 T A 44 rs62621197 19 8670147 ADAMTS10 C T 45 rs62134189 2 45046339 CAMKMT A G 46 rs2307111 5 75003678 POC5 T C 47 rs3936511 5 55860781 AC022431.2 A G 48 49 rs10234366 7 46743746 AC011294.3 G A 50 rs4808961 19 19577215 GATAD2A C G 51 rs117455294 20 57427951 GNAS C A 52 rs4267058 11 28645584 METTL15 T C 53 rs3013431 1 113242488 MOV10 C T 54 55 rs2867116 2 682363 TMEM18 C A 56 rs75387636 10 120278394 PRLHR G A 57 rs2281148 20 36433288 CTNNBL1 T C 58 rs10860295 12 98542699 RP11-181C3.1 T C 59 rs2902142 2 58849805 FANCL C T 60 rs10962279 9 16103030 CCDC171 T C

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1 2 rs12817542 12 103736499 C12orf42 C T 3 rs1852006 7 77829768 MAGI2 G A 4 rs10498713 6 22729300 HDGFL1 G T 5 rs6457808 6 35143465 TCP11 G T 6 7 rs7814267 8 5545084 CSMD1 A G 8 rs146980124 17 44627649 LRRC37A2 A C 9 rs8117463 20 17231063 PCSK2 G A 10 rs10953577 7 108263540 DNAJB9 T C 11 rs12748436 1 177761109 SEC16B C G 12 Confidential: For Review Only 13 rs4723263 7 33194826 BBS9 G C 14 rs7123283 11 122809055 C11orf63 C T 15 rs7145052 14 92461192 TRIP11 C T 16 rs67603370 17 7524504 SHBG G A 17 rs11891707 2 207120604 ZDBF2 T C 18 19 rs9652090 13 27983367 GTF3A G T 20 rs10842356 12 24621348 BCAT1 A T 21 rs62032001 16 49065630 CBLN1 A C 22 rs3993347 14 103267403 TRAF3 T C 23 rs7633995 3 180369750 CCDC39 A G 24 25 rs10116891 9 122651993 RP11-295D22.1 G A 26 rs636402 2 219466859 RQCD1 T C 27 rs884152 8 25770557 EBF2 G T 28 rs3118252 9 25115154 TUSC1 G C 29 rs6931604 6 98578215 POU3F2 C T 30 31 rs61936936 12 116391685 MED13L A T 32 rs9370527 6 56245812 COL21A1 G A 33 rs3181269 11 33755956 CD59 C T 34 rs9594686 13 42723197 DGKH C T 35 rs1666132 3 77649190 ROBO2 C T 36 37 rs4739558 8 38337264 FGFR1 A G 38 rs7354849 1 232765308 SIPA1L2 A G 39 rs9611560 22 41750622 ZC3H7B T C 40 rs7817581 8 143136114 TSNARE1 G A 41 rs7672 16 68294800 PLA2G15 C G 42 43 rs2242258 10 75607168 CAMK2G T C 44 rs1696058 12 90767159 CCER1 T C 45 rs7503580 17 79087036 BAIAP2 C T 46 rs115359679 7 755987 PRKAR1B C A 47 rs7711823 5 158489315 EBF1 A G 48 49 rs7565437 2 65646966 SPRED2 T C 50 rs11256627 10 10535954 CELF2 G A 51 rs11165687 1 97099767 PTBP2 C T 52 rs10937241 3 185822774 ETV5 A G 53 rs12941038 17 66509143 PRKAR1A C T 54 55 rs4545941 19 16534207 EPS15L1 T C 56 rs12308065 12 120624085 GCN1L1 A G 57 rs4783789 16 51446707 SALL1 T C 58 rs201666051 9 20920868 FOCAD C T 59 rs1476698 2 242296449 FARP2 A G 60 rs71483681 11 131469205 NTM T C

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1 2 rs2755253 1 67470843 SLC35D1 C T 3 rs7439324 4 44501351 KCTD8 C T 4 rs116293915 12 42705738 PPHLN1 C A 5 rs7163692 15 47932453 SEMA6D C G 6 7 rs1177279 2 61295122 KIAA1841 A G 8 rs6974282 7 100098295 NYAP1 C T 9 rs6577497 1 8605667 RERE A T 10 rs2539692 2 59841988 BCL11A T A 11 rs34722008 4 38659594 AC021860.1 G A 12 Confidential: For Review Only 13 rs1619120 9 87302196 NTRK2 A G 14 rs2958542 11 62181882 SCGB1A1 C T 15 rs10887571 10 88030441 GRID1 C T 16 rs115903965 3 66009529 MAGI1 G A 17 rs12132598 1 115235785 AMPD1 A G 18 19 rs2939931 10 121636406 MCMBP T C 20 rs3815156 17 29685150 NF1 A G 21 rs8130408 21 39237138 KCNJ6 A C 22 rs538579 3 62711674 CADPS G C 23 rs1061072 10 126684796 CTBP2 G A 24 25 rs7159126 14 93783176 BTBD7 T C 26 rs7217460 17 65393344 PITPNC1 G A 27 rs2268762 3 38516075 ACVR2B A G 28 rs1402989 3 27056851 NEK10 C T 29 rs7840305 8 57168101 CHCHD7 A G 30 31 rs10841379 12 19992303 AEBP2 A G 32 rs6719507 2 29733801 ALK G A 33 rs11727676 4 145659064 HHIP T C 34 rs73085586 20 22430241 FOXA2 G A 35 rs11925138 3 131626048 CPNE4 G A 36 37 rs11040333 11 49346332 FOLH1 G A 38 rs3791478 2 240064139 HDAC4 T C 39 rs10823504 10 72034062 NPFFR1 G A 40 rs594585 16 65939803 CDH5 T G 41 rs16839832 1 196349909 KCNT2 G T 42 43 rs76187039 6 43233990 TTBK1 G T 44 rs78420139 14 101201687 DLK1 G A 45 rs2175171 1 7028842 CAMTA1 G C 46 rs10791902 11 67093360 SSH3 C T 47 rs1000471 15 89986583 RHCG C T 48 49 rs4677156 3 72417857 RYBP A T 50 rs9610387 22 36476762 RBFOX2 G A 51 rs10503555 8 15763818 TUSC3 A G 52 rs12601380 17 34904985 GGNBP2 A C 53 rs1357798 3 83780583 CADM2 C T 54 55 rs10111937 8 54160092 OPRK1 C T 56 rs68015088 18 51484010 MBD2 G A 57 rs62048187 15 38117049 TMCO5A G C 58 rs3774604 3 53824136 CACNA1D C T 59 rs67679818 7 110672704 IMMP2L C T 60

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1 Supplementary Table 2: Genome-wide association study results for early2 life body size in the UK Biobank SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.596552 -0.04742 0.00142737 5.70E-242 8 0.794752 -0.04712 0.00173208 6.00E-163 9 0.513877 -0.03591 0.00139965 3.50E-145 10 0.951459 0.080205 0.00325367 3.60E-134 11 12 0.171864Confidential:-0.04335 0.00185227 For4.00E-121 Review Only 13 0.615537 -0.03126 0.00144009 1.60E-104 14 0.766595 -0.03328 0.00165555 6.80E-90 15 0.437703 0.02746 0.0014112 2.50E-84 16 0.565002 -0.0222 0.00141521 1.80E-55 17 18 0.857664 0.029855 0.00200515 3.90E-50 19 0.942407 -0.04234 0.00303598 3.30E-44 20 0.820086 -0.02501 0.00182377 8.30E-43 21 0.396432 -0.01834 0.0014277 8.80E-38 22 23 0.773633 0.021314 0.00167058 2.80E-37 24 0.586164 0.016651 0.00142402 1.40E-31 25 0.386247 -0.01648 0.00144207 3.00E-30 26 0.973981 -0.04841 0.00441228 5.20E-28 27 0.656346 -0.01576 0.00147894 1.60E-26 28 29 0.776056 -0.01782 0.00167858 2.50E-26 30 0.591453 -0.01456 0.00142183 1.30E-24 31 0.7406 -0.01623 0.00159852 3.10E-24 32 0.825618 -0.01894 0.00189383 1.50E-23 33 0.324953 -0.01474 0.00149539 6.40E-23 34 35 0.870646 -0.02063 0.00210607 1.20E-22 36 0.374865 0.014162 0.00144569 1.20E-22 37 0.975264 0.043985 0.00454379 3.70E-22 38 0.568979 -0.01374 0.00142539 5.30E-22 39 0.866272 -0.02013 0.00210974 1.40E-21 40 41 0.601978 -0.01365 0.00143018 1.40E-21 42 0.458349 -0.0135 0.00141729 1.70E-21 43 0.427582 0.013452 0.00141395 1.80E-21 44 0.523411 -0.01335 0.00140509 2.10E-21 45 0.640117 -0.01373 0.0014597 5.10E-21 46 47 0.737668 -0.01517 0.00161429 5.70E-21 48 0.961364 -0.03393 0.00364752 1.40E-20 49 0.873026 -0.01935 0.00211042 4.80E-20 50 0.491843 0.012897 0.00140787 5.20E-20 51 0.626072 0.013048 0.00144868 2.10E-19 52 53 0.676351 0.013379 0.00149777 4.20E-19 54 0.905761 0.021828 0.0024546 6.00E-19 55 0.784962 -0.01516 0.00170933 7.40E-19 56 0.656021 -0.01306 0.00147566 8.60E-19 57 0.894147 -0.02006 0.00227186 1.00E-18 58 59 0.797514 -0.01537 0.00174293 1.20E-18 60 0.898985 0.020604 0.00234116 1.40E-18 0.814942 0.015805 0.00180252 1.80E-18

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1 2 0.882895 -0.01906 0.00217729 2.00E-18 3 0.893449 -0.01999 0.00228695 2.30E-18 4 0.742436 -0.01394 0.00159845 2.70E-18 5 0.359636 0.012704 0.00145732 2.90E-18 6 7 0.673168 -0.01296 0.00149585 4.60E-18 8 0.561375 -0.01213 0.00142165 1.50E-17 9 0.654054 -0.01257 0.00147501 1.60E-17 10 0.65069 0.012536 0.00147235 1.70E-17 11 0.622962 0.012342 0.0014507 1.80E-17 12 Confidential: For Review Only 13 0.305175 -0.01291 0.00152339 2.30E-17 14 0.178094 0.015449 0.00183012 3.10E-17 15 0.79024 -0.0145 0.00171845 3.20E-17 16 0.389639 0.012068 0.00143825 4.80E-17 17 0.131408 -0.01753 0.00210763 9.00E-17 18 19 0.980505 0.042032 0.00509751 1.60E-16 20 0.502937 -0.01156 0.00140654 2.00E-16 21 0.967498 -0.03225 0.00394917 3.20E-16 22 0.404079 -0.01185 0.00145793 4.40E-16 23 0.933673 -0.02284 0.00281497 4.90E-16 24 25 0.757269 0.013237 0.00163438 5.50E-16 26 0.599358 -0.01156 0.00142927 6.20E-16 27 0.652316 0.011864 0.00147086 7.30E-16 28 0.68227 0.012151 0.00150731 7.50E-16 29 0.808677 0.014354 0.0017812 7.70E-16 30 31 0.626428 -0.01171 0.00145885 1.00E-15 32 0.706844 0.012289 0.00154345 1.70E-15 33 0.31586 0.012067 0.00152242 2.30E-15 34 0.888558 -0.01763 0.00222464 2.30E-15 35 0.503174 0.01107 0.00140256 3.00E-15 36 37 0.670052 0.011691 0.00148697 3.80E-15 38 0.715873 -0.01219 0.00155483 4.40E-15 39 0.885665 0.017187 0.00219676 5.10E-15 40 0.798517 -0.01367 0.00175094 5.90E-15 41 0.365603 -0.01134 0.00145639 6.90E-15 42 43 0.37581 -0.01118 0.00144458 1.00E-14 44 0.766455 -0.01272 0.001658 1.70E-14 45 0.63966 0.011053 0.00145717 3.30E-14 46 0.723747 0.011868 0.00156406 3.30E-14 47 0.506779 -0.01064 0.00140318 3.40E-14 48 49 0.931102 -0.02096 0.00277071 3.90E-14 50 0.601401 -0.01091 0.0014437 4.20E-14 51 0.841645 -0.01538 0.00204209 5.00E-14 52 0.184152 0.013543 0.00180308 5.90E-14 53 0.35132 0.011087 0.00147962 6.70E-14 54 55 0.717446 0.011646 0.0015571 7.50E-14 56 0.715936 -0.01167 0.0015618 7.80E-14 57 0.367072 -0.0109 0.0014606 8.50E-14 58 0.942918 -0.02248 0.00301599 9.00E-14 59 0.258487 -0.01209 0.00162629 1.00E-13 60 0.902215 0.017501 0.00236302 1.30E-13

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1 2 0.953645 -0.02458 0.00333076 1.60E-13 3 0.92759 -0.01974 0.00269425 2.30E-13 4 0.585662 0.010349 0.0014216 3.40E-13 5 0.839907 -0.01885 0.00259515 3.80E-13 6 7 0.520764 -0.01024 0.00141773 5.20E-13 8 0.77367 -0.01231 0.00170539 5.30E-13 9 0.113398 -0.01591 0.00220637 5.60E-13 10 0.51711 -0.01012 0.00140546 6.10E-13 11 0.628088 -0.01039 0.00144907 7.50E-13 12 Confidential: For Review Only 13 0.654505 0.010517 0.00147302 9.40E-13 14 0.47969 0.009966 0.00141056 1.60E-12 15 0.671971 0.010529 0.00149263 1.70E-12 16 0.955251 -0.02388 0.00338464 1.70E-12 17 0.19996 0.012354 0.00175019 1.70E-12 18 19 0.393414 -0.01015 0.00143978 1.80E-12 20 0.335053 -0.01051 0.0014958 2.10E-12 21 0.657832 -0.01039 0.00148319 2.40E-12 22 0.773702 0.011723 0.00167816 2.80E-12 23 0.698774 -0.01062 0.00152472 3.30E-12 24 25 0.669786 0.010341 0.00149388 4.50E-12 26 0.627782 -0.01006 0.00145817 5.30E-12 27 0.411293 -0.0098 0.00142677 6.50E-12 28 0.62244 -0.00994 0.00144891 6.80E-12 29 0.44025 -0.00967 0.00141008 7.00E-12 30 31 0.414981 -0.00974 0.00142581 8.40E-12 32 0.282112 -0.01062 0.00156177 1.00E-11 33 0.357105 0.009927 0.00146237 1.10E-11 34 0.735103 -0.01075 0.00158832 1.30E-11 35 0.630603 0.009805 0.00145108 1.40E-11 36 37 0.682031 -0.01017 0.00150615 1.50E-11 38 0.893663 -0.01541 0.00228414 1.50E-11 39 0.593282 0.009582 0.00142532 1.80E-11 40 0.49204 0.009381 0.00139994 2.10E-11 41 0.503006 -0.00942 0.00140949 2.30E-11 42 43 0.299591 0.01034 0.00154965 2.50E-11 44 0.866936 0.013754 0.00206148 2.50E-11 45 0.80578 0.01179 0.00176862 2.60E-11 46 0.684557 -0.01004 0.00150806 2.80E-11 47 0.978757 0.033417 0.00502526 2.90E-11 48 49 0.321912 -0.00998 0.00149947 2.90E-11 50 0.327748 0.010099 0.0015214 3.20E-11 51 0.465213 -0.00931 0.00140401 3.30E-11 52 0.762745 0.01088 0.00164522 3.80E-11 53 0.442849 0.009314 0.00141068 4.00E-11 54 55 0.679324 -0.01046 0.00158456 4.10E-11 56 0.840611 -0.01268 0.0019229 4.30E-11 57 0.686864 0.009887 0.00150652 5.30E-11 58 0.517857 0.009154 0.00140367 7.00E-11 59 0.343455 -0.00959 0.00147352 7.70E-11 60 0.683074 -0.01079 0.00167142 1.10E-10

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1 2 0.702174 0.01002 0.0015532 1.10E-10 3 0.435592 0.009091 0.00141564 1.30E-10 4 0.637545 0.009371 0.00146096 1.40E-10 5 0.199337 0.0113 0.00176862 1.70E-10 6 7 0.737635 -0.01012 0.00158868 1.90E-10 8 0.87821 -0.01377 0.0021645 2.00E-10 9 0.512551 0.009024 0.00141867 2.00E-10 10 0.72267 0.009956 0.00156699 2.10E-10 11 0.556491 0.00893 0.00140744 2.20E-10 12 Confidential: For Review Only 13 0.794818 0.011108 0.00174972 2.20E-10 14 0.553108 0.008942 0.00141021 2.30E-10 15 0.283869 -0.00988 0.00155984 2.40E-10 16 0.735808 0.010049 0.00158821 2.50E-10 17 0.558438 -0.00896 0.00142043 2.80E-10 18 19 0.935497 0.018081 0.00286728 2.90E-10 20 0.235517 0.010539 0.00167252 3.00E-10 21 0.906093 -0.0151 0.0024091 3.60E-10 22 0.22119 -0.0106 0.00169243 3.80E-10 23 0.852214 -0.01237 0.00197676 3.90E-10 24 25 0.623257 -0.00908 0.00145444 4.30E-10 26 0.501462 0.008744 0.00140147 4.40E-10 27 0.708124 -0.00966 0.00154965 4.60E-10 28 0.547323 -0.00882 0.00141558 4.70E-10 29 0.252094 -0.01005 0.00161541 4.90E-10 30 31 0.36595 0.009088 0.00146255 5.20E-10 32 0.829486 -0.01155 0.00186108 5.40E-10 33 0.708451 -0.00956 0.00154078 5.50E-10 34 0.627856 0.00899 0.0014507 5.70E-10 35 0.343693 0.00917 0.00148232 6.20E-10 36 37 0.76914 0.010212 0.00166271 8.20E-10 38 0.479203 -0.00858 0.00139949 8.80E-10 39 0.22577 0.010285 0.00167804 8.80E-10 40 0.672558 0.009307 0.00151981 9.10E-10 41 0.791515 0.010617 0.00173406 9.20E-10 42 43 0.398321 0.008753 0.0014312 9.60E-10 44 0.962835 -0.02353 0.0038478 9.60E-10 45 0.896658 0.014197 0.00232462 1.00E-09 46 0.604907 0.008736 0.00143344 1.10E-09 47 0.808037 0.010831 0.00177725 1.10E-09 48 49 0.895237 -0.01396 0.0022919 1.10E-09 50 0.633254 0.008899 0.00145843 1.10E-09 51 0.948721 0.019321 0.00317271 1.10E-09 52 0.626467 0.008786 0.00144632 1.20E-09 53 0.388477 0.008705 0.00143466 1.30E-09 54 55 0.860357 -0.01227 0.00202796 1.40E-09 56 0.958457 -0.02122 0.00350991 1.50E-09 57 0.749285 -0.00979 0.00161914 1.50E-09 58 0.55235 -0.00852 0.00141032 1.60E-09 59 0.625064 0.008713 0.00144593 1.70E-09 60 0.781672 -0.01019 0.00169453 1.80E-09

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1 2 0.939168 -0.0176 0.00292738 1.80E-09 3 0.64299 0.008773 0.00146122 1.90E-09 4 0.850669 -0.01178 0.00196504 2.00E-09 5 0.981979 -0.0315 0.00526278 2.20E-09 6 7 0.81462 -0.01089 0.00182656 2.50E-09 8 0.383726 0.010241 0.00172485 2.90E-09 9 0.675262 0.0089 0.00149889 2.90E-09 10 0.623364 -0.00858 0.00144701 3.00E-09 11 0.9237 -0.01561 0.002642 3.50E-09 12 Confidential: For Review Only 13 0.566915 -0.00833 0.00141275 3.70E-09 14 0.525219 0.008322 0.00141117 3.70E-09 15 0.549319 -0.00831 0.00140944 3.70E-09 16 0.921665 -0.01583 0.00268431 3.70E-09 17 0.864826 0.012105 0.00205431 3.80E-09 18 19 0.540322 -0.00833 0.00141558 4.00E-09 20 0.484602 0.008234 0.00140036 4.10E-09 21 0.802785 -0.0104 0.00176942 4.20E-09 22 0.352881 0.008615 0.00146845 4.40E-09 23 0.899338 -0.01448 0.00247597 4.90E-09 24 25 0.89905 -0.0136 0.00233545 5.80E-09 26 0.395066 0.008329 0.00143111 5.90E-09 27 0.355895 -0.00851 0.00146322 6.00E-09 28 0.416563 -0.00832 0.00142927 6.00E-09 29 0.398855 -0.00833 0.0014327 6.20E-09 30 31 0.900038 -0.01362 0.00234396 6.20E-09 32 0.759058 -0.00949 0.00163571 6.40E-09 33 0.745591 0.009327 0.0016066 6.40E-09 34 0.823184 0.010701 0.00184282 6.40E-09 35 0.422104 0.008273 0.00142698 6.70E-09 36 37 0.399483 0.008295 0.00143069 6.70E-09 38 0.540843 -0.00817 0.00141027 6.80E-09 39 0.261198 0.009309 0.00161153 7.60E-09 40 0.67229 0.008612 0.00149135 7.70E-09 41 0.285863 0.009004 0.00156003 7.90E-09 42 43 0.741068 -0.0092 0.00159781 8.50E-09 44 0.402699 0.008391 0.00145752 8.60E-09 45 0.841844 -0.01112 0.00193305 8.90E-09 46 0.930782 -0.01643 0.00285935 9.20E-09 47 0.637547 0.008388 0.00146043 9.30E-09 48 49 0.590225 0.008183 0.00142584 9.50E-09 50 0.295322 -0.00888 0.00154651 9.50E-09 51 0.590832 -0.00813 0.001421 1.00E-08 52 0.160567 -0.01091 0.00190978 1.10E-08 53 0.769815 -0.00954 0.00166872 1.10E-08 54 55 0.831369 -0.01088 0.00190325 1.10E-08 56 0.373043 -0.00829 0.00145482 1.20E-08 57 0.777678 0.009583 0.00168296 1.20E-08 58 0.618198 -0.00824 0.0014494 1.30E-08 59 0.631534 0.008222 0.0014496 1.40E-08 60 0.487454 -0.00806 0.00142109 1.40E-08

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1 2 0.291714 0.008712 0.00153927 1.50E-08 3 0.837732 0.010771 0.0019031 1.50E-08 4 0.555071 -0.008 0.00141326 1.50E-08 5 0.649385 0.008311 0.00146823 1.50E-08 6 7 0.2779 0.008831 0.00156428 1.60E-08 8 0.804155 0.010056 0.00177805 1.60E-08 9 0.614272 0.008072 0.00143424 1.80E-08 10 0.391021 0.008073 0.00143311 1.80E-08 11 0.646531 0.008265 0.00146755 1.80E-08 12 Confidential: For Review Only 13 0.399349 -0.00806 0.00143197 1.80E-08 14 0.632298 0.008239 0.00146406 1.80E-08 15 0.552146 -0.00798 0.00141952 1.90E-08 16 0.975613 -0.02551 0.00454393 2.00E-08 17 0.667322 -0.00832 0.00148685 2.20E-08 18 19 0.517188 -0.00786 0.00140343 2.20E-08 20 0.82365 -0.01031 0.00184428 2.30E-08 21 0.255786 -0.00901 0.00161364 2.30E-08 22 0.685061 -0.00842 0.00150934 2.40E-08 23 0.892937 0.012677 0.00227298 2.40E-08 24 25 0.716531 0.008679 0.00155446 2.40E-08 26 0.770482 0.009368 0.00167795 2.40E-08 27 0.388067 -0.00799 0.00143606 2.60E-08 28 0.514974 -0.00779 0.00140203 2.70E-08 29 0.62892 0.008059 0.00144985 2.70E-08 30 31 0.315325 -0.00839 0.00150927 2.70E-08 32 0.558383 0.007818 0.00140961 2.90E-08 33 0.903565 0.013146 0.00237141 3.00E-08 34 0.798751 -0.00971 0.0017522 3.00E-08 35 0.904169 0.013234 0.00238955 3.10E-08 36 37 0.290309 -0.00855 0.00154462 3.10E-08 38 0.890549 0.012509 0.00226474 3.30E-08 39 0.936321 0.015862 0.0028729 3.40E-08 40 0.408838 0.007951 0.0014401 3.40E-08 41 0.917759 -0.01408 0.00255407 3.50E-08 42 43 0.865193 -0.01131 0.00205092 3.50E-08 44 0.944649 0.017042 0.00309099 3.50E-08 45 0.443375 -0.00777 0.00140957 3.60E-08 46 0.58767 -0.00791 0.00143682 3.60E-08 47 0.783832 -0.00951 0.00172531 3.60E-08 48 49 0.230804 0.009246 0.00167959 3.70E-08 50 0.914436 0.013799 0.00250771 3.70E-08 51 0.5568 0.007777 0.00141489 3.90E-08 52 0.587339 0.007798 0.00141888 3.90E-08 53 0.213947 -0.00939 0.00171142 4.10E-08 54 55 0.699952 -0.00837 0.00152827 4.30E-08 56 0.654098 0.008104 0.00147879 4.30E-08 57 0.682898 -0.00839 0.00153213 4.40E-08 58 0.631085 0.007935 0.00145441 4.90E-08 59 0.417621 0.007797 0.00142961 4.90E-08 60

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1 2 Supplementary Table 3: Genome-wide association study results for adulthood body size in the UK Biobank 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs56094641 16 53806453 FTO A G 8 rs58084604 18 57849429 MC4R C T 9 rs374892365 2 633055 TMEM18 A T 10 rs539515 1 177889025 SEC16B A C 11 12 rs563738408Confidential:2 420443 ForFAM150B ReviewG OnlyA 13 rs6752378 2 25150116 ADCY3 C A 14 rs6265 11 27679916 BDNF C T 15 rs72892910 6 50816887 TFAP2B G T 16 rs12507026 4 45181334 GNPDA2 A T 17 18 rs7132908 12 50263148 FAIM2 G A 19 rs9843653 3 49920571 MST1R T C 20 rs7498665 16 28883241 SH2B1 A G 21 rs10423928 19 46182304 GIPR T A 22 23 rs2307111 5 75003678 POC5 T C 24 rs9366863 6 34688946 C6orf106 T C 25 rs34517439 1 78450517 DNAJB4 C A 26 rs2241420 15 68082816 MAP2K5 G A 27 rs13107325 4 103188709 SLC39A8 C T 28 29 rs12798028 11 47604639 NDUFS3 C T 30 rs3810291 19 47569003 ZC3H4 G A 31 rs3814883 16 29994922 TAOK2 C T 32 rs2613499 1 72751552 NEGR1 A G 33 rs17770336 9 28414625 LINGO2 C T 34 35 rs2678204 1 201800511 IPO9 T G 36 rs869400 3 185826740 ETV5 T G 37 rs862320 16 69651866 NFAT5 C T 38 rs59227842 11 43692423 HSD17B12 A G 39 rs34811474 4 25408838 ANAPC4 G A 40 41 rs7424120 2 59313974 FANCL C T 42 rs34898535 16 31025641 STX1B C T 43 rs879620 16 4015729 ADCY9 C T 44 rs236660 7 75050086 POM121C T C 45 rs1320903 3 131758077 CPNE4 G A 46 47 rs57636386 18 58048295 MC4R T C 48 rs1477290 5 87988934 MEF2C T C 49 rs41279738 1 110082551 GPR61 T G 50 rs12429545 13 54102206 OLFM4 G A 51 rs10146997 14 79945162 NRXN3 A G 52 53 rs4671328 2 58935282 FANCL T G 54 rs17716502 8 116659731 TRPS1 C T 55 rs11150745 17 78757626 RPTOR A G 56 rs6575340 14 94023972 UNC79 G A 57 rs1788808 18 21090023 NPC1 A G 58 59 rs12253527 10 21819824 MLLT10 G A 60 rs147730268 12 123024476 KNTC1 G T rs34298980 6 40409243 LRFN2 T C

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1 2 rs35957544 8 73440371 KCNB2 G T 3 rs3748126 7 76632736 UPK3B C G 4 rs13292699 9 15910044 CCDC171 A C 5 rs61813324 1 156049877 MEX3A C T 6 7 rs12883788 14 33303540 AKAP6 C T 8 rs2234458 11 65639374 EFEMP2 C T 9 rs66460909 20 51195387 ZFP64 G A 10 rs1454687 3 94038085 NSUN3 C G 11 rs1320251 17 21264396 KCNJ12 C T 12 Confidential: For Review Only 13 rs12140153 1 62579891 INADL G T 14 rs10404726 19 18834514 CRTC1 C T 15 rs12484438 22 40558064 TNRC6B T C 16 rs403694 21 46567625 ADARB1 C T 17 rs12357890 10 99762693 CRTAC1 A G 18 19 rs8054082 16 19975418 GPR139 C T 20 rs9788550 14 29681138 PRKD1 G C 21 rs8015400 14 25930988 STXBP6 C A 22 rs4790292 17 1824305 RTN4RL1 C A 23 rs2260051 6 31591918 PRRC2A A T 24 25 rs1296328 4 137083193 PCDH18 A C 26 rs55896564 8 11447093 BLK G A 27 rs429358 19 45411941 APOE T C 28 rs6938973 6 98421721 MMS22L T C 29 rs6601451 8 10243681 MSRA C G 30 31 rs11134679 5 170623391 RANBP17 A G 32 rs200119412 8 77224420 ZFHX4 T C 33 rs11079849 17 47090785 IGF2BP1 C T 34 rs6679458 1 96946253 PTBP2 G T 35 rs1167311 1 49996959 AGBL4 G A 36 37 rs6870983 5 87697533 TMEM161B C T 38 rs409696 2 147900651 ACVR2A G A 39 rs9317002 13 59175727 PCDH17 C A 40 rs2206925 20 6634895 BMP2 T C 41 rs149457 5 107438057 FBXL17 C T 42 43 rs28711392 11 13349559 ARNTL T C 44 rs7827182 8 8380471 SGK223 G C 45 rs55726687 12 991306 WNK1 G A 46 rs4764949 12 103658096 C12orf42 A G 47 rs113230003 19 18460956 PGPEP1 G A 48 49 rs1576655 13 79587841 RBM26 A C 50 rs7145882 14 103255461 TRAF3 T C 51 rs11691869 2 100805996 AFF3 C A 52 rs6445198 3 61219865 FHIT G T 53 rs1568488 3 153657951 ARHGEF26 G C 54 55 rs72976986 19 4050424 ZBTB7A G A 56 rs11496125 7 103417557 RELN C T 57 rs1631026 2 26953850 KCNK3 C T 58 rs12462975 19 30272202 CCNE1 G A 59 rs815163 1 190294726 BRINP3 T C 60 rs12538826 7 99030228 PTCD1 T C

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1 2 rs8192675 3 170724883 SLC2A2 T C 3 rs41310284 10 102447647 PAX2 C A 4 rs6669341 1 47678458 TAL1 A G 5 rs4759228 12 56508409 PA2G4 G C 6 7 rs67257872 11 8530218 STK33 A G 8 rs12951079 17 34933059 GGNBP2 G A 9 rs115866895 1 1592638 SLC35E2B A G 10 rs7553158 1 75005238 TNNI3K G A 11 rs61217499 12 108417780 WSCD2 G C 12 Confidential: For Review Only 13 rs217672 14 62361021 SYT16 A C 14 rs10805383 5 63034606 HTR1A G A 15 rs183315407 1 46201427 IPP G A 16 rs11633022 15 73074890 ADPGK C A 17 rs12477088 2 67841326 ETAA1 T C 18 19 rs11915747 3 85699040 CADM2 C G 20 rs3737992 1 33234128 KIAA1522 G A 21 rs9277992 6 33312455 DAXX G A 22 rs529200 3 173114305 NLGN1 A G 23 rs12149660 16 70309237 AARS G A 24 25 rs62261477 3 48779421 IP6K2 G C 26 rs2253310 6 108888593 FOXO3 C G 27 rs724623 14 47303577 MDGA2 A C 28 rs73213484 4 28489339 RP11-180C1.1 A T 29 rs1222216 11 30346052 ARL14EP C T 30 31 rs34994596 15 80991447 ABHD17C T C 32 rs4658403 1 243832560 AKT3 C T 33 rs35809007 2 47019521 LINC01118 G A 34 rs1327259 6 51177811 PKHD1 A G 35 rs58243949 18 52509833 RAB27B C T 36 37 rs73026723 19 31017177 ZNF536 C T 38 rs215634 7 32369148 PDE1C A G 39 rs412243 16 339672 AXIN1 T C 40 rs10756555 9 14459089 NFIB G A 41 rs2343681 3 136535024 SLC35G2 G A 42 43 rs2237025 4 55541879 KIT T C 44 rs112253053 19 19425145 SUGP1 T A 45 rs34388845 6 28578286 SCAND3 A G 46 rs4482463 2 205375909 PARD3B C A 47 rs2035936 3 141298124 RASA2 G T 48 49 rs10174253 2 181323160 CWC22 A C 50 rs35193668 13 33092929 N4BP2L2 C T 51 rs6798941 3 52893465 TMEM110 C T 52 rs3931548 9 103113652 TEX10 C A 53 rs273505 19 18217147 MAST3 T C 54 55 rs13329943 16 24733751 TNRC6A C T 56 rs111768603 3 42329113 CCK G T 57 rs10821196 9 96433396 PHF2 G A 58 rs4962725 10 126733321 CTBP2 T C 59 rs61903695 11 89922417 NAALAD2 A G 60 rs3753639 1 154986091 ZBTB7B T C

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1 2 rs2433733 2 230816703 FBXO36 G A 3 rs1967772 13 28036062 MTIF3 G A 4 rs59893724 5 80830788 SSBP2 A G 5 rs11607476 11 115037061 CADM1 A C 6 7 rs1477890 4 18511738 LCORL A G 8 rs2396625 7 113028634 TSRM T A 9 rs57488047 15 79403002 RASGRF1 T C 10 rs4648450 1 2723214 TTC34 C A 11 rs1451533 2 105466005 POU3F3 G A 12 Confidential: For Review Only 13 rs809955 4 140874760 MAML3 G A 14 rs1632887 6 29909217 HLA-A T G 15 rs2056477 7 2079744 MAD1L1 G C 16 rs55931203 17 65854602 BPTF C T 17 rs28350 3 42418446 LYZL4 A G 18 19 rs12072739 1 98315893 DPYD A G 20 rs1840660 7 114352615 FOXP2 G A 21 rs1411432 9 16728532 BNC2 A C 22 rs9579775 13 20616557 ZMYM2 A C 23 rs7924036 10 65191645 JMJD1C G T 24 25 rs9515446 13 112217108 RP11-65D24.2 A G 26 rs13174863 5 139080745 CXXC5 A G 27 rs112852122 20 47498117 ARFGEF2 G A 28 rs7893571 10 16750129 RSU1 G T 29 rs1582931 5 122657199 CEP120 G A 30 31 rs1436348 3 104612668 ALCAM A G 32 rs1778830 1 156489974 IQGAP3 G A 33 rs7601895 2 55281901 RTN4 C G 34 rs1805123 7 150645534 KCNH2 T G 35 rs2289379 7 44804225 ZMIZ2 C T 36 37 rs12788343 11 131452912 NTM T C 38 rs12033257 1 112318484 KCND3 A G 39 rs7433076 3 90234502 EPHA3 T A 40 rs2583410 4 102182199 PPP3CA A C 41 rs36007635 6 163009335 PARK2 G A 42 43 rs2035806 10 133984916 JAKMIP3 G A 44 rs71495049 10 34014435 PARD3 G A 45 rs61992671 14 101531854 AL117190.3 A G 46 rs2875762 6 124925032 NKAIN2 G C 47 rs1547026 6 51825622 PKHD1 T C 48 49 rs10799778 1 23313353 LACTBL1 T G 50 rs34292685 11 64049021 GPR137 C T 51 rs396354 2 86850022 CHMP3 T C 52 rs75499503 6 26145217 HIST1H2AC C T 53 rs2051559 4 3298800 RGS12 T C 54 55 rs6963840 7 78144371 MAGI2 C T 56 rs329118 5 133861663 JADE2 C T 57 rs12427047 12 90213070 ATP2B1 C T 58 rs4527444 4 30842780 PCDH7 A G 59 rs3759584 14 103990799 CKB T C 60 rs11782074 8 142617096 AC138647.1 G T

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1 2 rs2114210 8 95595162 KIAA1429 G A 3 rs58351927 17 5297038 NUP88 A G 4 rs6050446 20 25195509 ENTPD6 A G 5 rs6761463 2 50201547 NRXN1 G C 6 7 rs1458156 12 41887940 PDZRN4 C T 8 rs7038966 9 73777777 TRPM3 C T 9 rs559231 18 39644247 PIK3C3 G T 10 rs61909165 11 134589355 AP003062.1 T A 11 rs7719067 5 153538241 MFAP3 A G 12 Confidential: For Review Only 13 rs4759073 12 54653258 CBX5 G A 14 rs2725371 8 30854033 PURG A G 15 rs187067151 20 29539588 FRG1B G T 16 rs62277889 2 198783693 PLCL1 C T 17 rs114593013 3 84113491 CADM2 A G 18 19 rs2712667 12 99588917 ANKS1B G C 20 rs17029006 3 12329452 PPARG C T 21 rs9522180 13 111970212 TEX29 C T 22 rs9421249 10 118623322 ENO4 C T 23 rs7206608 16 82872628 CDH13 C G 24 25 rs6507054 18 31248323 ASXL3 T C 26 rs4148155 4 89054667 ABCG2 A G 27 rs7103389 11 881639 CHID1 T C 28 rs61971082 13 86494667 SLITRK6 T G 29 rs11000993 10 76084111 ADK T C 30 31 rs4806814 19 1860147 KLF16 G A 32 rs7519259 1 66434743 PDE4B G A 33 rs6606686 12 110903380 GPN3 G C 34 rs1373349 18 63282992 CDH7 C T 35 rs7749708 6 153375907 RGS17 C T 36 37 rs9477762 6 18507853 RNF144B A T 38 rs7321285 13 54319327 OLFM4 A C 39 rs72910629 6 69761994 BAI3 A G 40 rs27215 5 66219318 MAST4 C A 41 rs7990098 13 96982541 HS6ST3 T G 42 43 rs116195355 1 39941508 MACF1 C A 44 rs788163 2 172931559 METAP1D A C 45 rs9395520 6 13183523 PHACTR1 C T 46 rs17399739 10 87490850 GRID1 A G 47 rs78369934 17 61739101 MAP3K3 T C 48 49 rs7925100 11 118941596 VPS11 G A 50 rs544200874 4 20124826 SLIT2 C T 51 rs80082351 3 114415926 ZBTB20 A G 52 rs72917533 2 175238924 CIR1 T C 53 rs113962925 17 46044446 CDK5RAP3 C T 54 55 rs4916229 1 171443368 PRRC2C C G 56 rs4575195 10 114765747 TCF7L2 C A 57 rs76824303 3 62459819 CADPS A C 58 rs12187066 5 88800355 MEF2C A G 59 rs10499014 6 97947755 MMS22L C G 60 rs113132247 9 131026108 GOLGA2 G A

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1 2 rs3902951 14 69789755 GALNT16 T G 3 rs67913249 5 43204126 NIM1K C G 4 rs2866720 7 70106310 AUTS2 C T 5 rs117176448 8 27261138 PTK2B C G 6 7 rs13218383 6 120173501 MAN1A1 C G 8 rs11525873 7 138817193 TTC26 T C 9 rs10185199 2 40282202 SLC8A1 G A 10 rs151252883 2 228998026 SPHKAP T G 11 rs2952863 4 130759647 C4orf33 T G 12 Confidential: For Review Only 13 rs7038943 9 120377178 TLR4 T C 14 rs329651 11 133767622 IGSF9B G T 15 rs347551 5 119389031 PRR16 C G 16 rs698147 5 3513485 IRX1 A G 17 rs2237402 7 39449768 POU6F2 G A 18 19 rs6843852 4 162132758 FSTL5 C T 20 rs4467770 6 12086826 HIVEP1 G A 21 rs556992087 12 124500725 FAM101A T C 22 rs78508049 1 210344884 SYT14 T C 23 rs262956 3 183486117 YEATS2 T G 24 25 rs6583310 3 196170985 UBXN7 G C 26 rs28839214 4 145313641 GYPA G T 27 rs7619139 3 25110415 RARB T A 28 rs12147845 14 101144596 DLK1 C T 29 rs7182917 15 52080803 TMOD2 T C 30 31 rs36131051 3 107888841 IFT57 T G 32 rs1598121 3 82694710 GBE1 A G 33 rs11223204 11 132652554 OPCML A G 34 rs113569731 3 47093206 SETD2 C A 35 rs72652703 8 67209548 CRH T C 36 37 rs12213441 6 143208838 HIVEP2 C T 38 rs72673947 8 118884379 EXT1 A G 39 rs6530737 8 14095763 SGCZ A G 40 rs7030609 9 129415775 LMX1B A G 41 rs8011566 14 42939471 LRFN5 T A 42 43 rs10760277 9 126093999 CRB2 C T 44 rs369461388 14 40104718 FBXO33 G C 45 rs845084 10 125220036 GPR26 G A 46 rs9478496 6 154333183 OPRM1 T C 47 rs10736156 10 104019447 GBF1 C A 48 49 rs8038574 15 95275890 MCTP2 T C 50 rs7230240 18 42597978 SETBP1 C T 51 rs10749659 1 151033979 MLLT11 C T 52 rs811054 16 72251132 PMFBP1 C T 53 rs4971239 1 203491150 OPTC G A 54 55 rs6030803 20 41986507 SRSF6 T C 56 rs10791113 11 130873165 SNX19 A G 57 rs12927792 16 9713194 RP11-297M9.1 C T 58 rs10204994 2 35443726 CRIM1 G A 59 rs55658481 2 219284215 VIL1 G A 60 rs11701433 21 40296411 ETS2 C T

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1 2 rs4858940 3 88254820 C3orf38 T C 3 rs13104584 4 80811227 ANTXR2 G A 4 rs7549358 1 115252609 NRAS G C 5 rs1852006 7 77829768 MAGI2 G A 6 7 rs6075658 20 2094078 STK35 T C 8 rs10969334 9 29717279 LINGO2 C A 9 rs7264802 20 62692440 TCEA2 A G 10 rs77560793 1 175001179 MRPS14 G A 11 rs10927006 1 243557659 SDCCAG8 T C 12 Confidential: For Review Only 13 rs9834519 3 156379637 TIPARP C T 14 rs667515 11 69449076 CCND1 G C 15 rs1286138 14 91485445 RPS6KA5 T G 16 rs78886584 1 16859325 FAM231B A G 17 rs62171698 2 143959096 ARHGAP15 C A 18 19 rs201475383 20 26273991 FAM182B G A 20 rs544957562 9 33978015 UBAP2 A T 21 rs28726372 1 84353839 TTLL7 T C 22 rs114728753 3 78483402 ROBO1 A C 23 rs79236537 5 86727690 CCNH G T 24 25 rs1250597 10 81010250 ZMIZ1 A G 26 rs45521740 19 2245622 SF3A2 G A 27 rs60497719 19 33971746 PEPD G A 28 rs533493779 2 104447054 TMEM182 A T 29 rs6752979 2 81741750 CTNNA2 G A 30 31 rs10935143 3 134665159 EPHB1 G A 32 rs113706999 3 44159156 TOPAZ1 T A 33 rs10505836 12 19288508 PLEKHA5 A C 34 rs2425856 20 44911954 CDH22 A G 35 rs7102934 11 84648068 DLG2 T C 36 37 rs13427822 2 213414265 ERBB4 A G 38 rs112380819 3 9498519 SETD5 G A 39 rs13061117 3 181186466 SOX2 T C 40 rs80082536 3 35195311 ARPP21 A G 41 rs6597653 9 133788465 FIBCD1 G C 42 43 rs12281009 11 117032959 PAFAH1B2 A G 44 rs62259692 3 51847709 IQCF3 G A 45 rs80236973 3 188001014 LPP C T 46 rs62004865 15 74207695 LOXL1 T A 47 rs4737188 8 64756657 YTHDF3 A T 48 49 rs512121 18 7548501 PTPRM T C 50 rs945211 1 32191798 BAI2 G C 51 rs12926506 16 81722413 CMIP C T 52 rs16940823 18 22137319 HRH4 C A 53 rs13186637 5 153108558 GRIA1 T C 54 55 rs55838622 5 95711605 PCSK1 A C 56 rs181617194 12 122011598 KDM2B T C 57 rs2516726 16 2095065 NTHL1 T C 58 rs9673839 16 76895693 RP11-58C22.1 A G 59 rs473837 8 60906881 CA8 G T 60 rs2616143 8 20632022 LZTS1 G A

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1 2 rs6478538 9 124627012 TTLL11 A G 3 rs76520838 15 47916618 SEMA6D C T 4 rs11659764 18 53335512 TCF4 T A 5 rs76702514 1 195148296 KCNT2 C G 6 7 rs7548936 1 91207757 BARHL2 G C 8 rs252749 5 77389973 AP3B1 G A 9 rs7331420 13 99236471 STK24 G A 10 rs61985411 14 41336102 LRFN5 T A 11 rs3806114 6 20482335 E2F3 G A 12 Confidential: For Review Only 13 rs4911382 20 32553095 RALY C T 14 rs738140 22 41884954 ACO2 A G 15 rs2974550 5 152053480 NMUR2 T G 16 rs156126 6 104810083 HACE1 T C 17 rs78565420 8 85703065 RALYL C T 18 19 rs61954177 13 40787036 AL133318.1 G C 20 rs12517187 5 112444682 MCC C T 21 rs2074686 7 100800635 AP1S1 G A 22 rs4836133 5 124332103 ZNF608 C A 23 rs11150462 16 82451679 CDH13 T A 24 25 rs575840515 1 80796649 LPHN2 A G 26 rs7498044 15 92573639 SLCO3A1 G A 27 rs79675564 2 211286896 LANCL1 C A 28 rs11856579 15 78012688 LINGO1 G A 29 rs9852062 3 45373442 LARS2 T A 30 31 rs567230078 6 43588227 GTPBP2 T A 32 rs149778057 13 31007805 HMGB1 A C 33 rs61746970 19 51132746 SYT3 G A 34 rs78517245 3 42587865 SEC22C T C 35 rs13275517 8 143364521 TSNARE1 T C 36 37 rs112875651 8 126506694 TRIB1 G A 38 rs9507791 13 27352678 GPR12 G A 39 rs9496567 6 100602753 MCHR2 G A 40 rs1704190 2 200760629 C2orf69 G A 41 rs1040046 6 83473573 UBE3D C A 42 43 rs7752998 6 34398358 RPS10 A T 44 rs12031634 1 34584393 CSMD2 G A 45 rs4792716 17 15943144 NCOR1 A G 46 rs2837398 21 41427168 DSCAM A C 47 rs35852935 4 17991522 LCORL A C 48 49 rs9480184 6 155987788 NOX3 C T 50 rs11864909 16 20400839 PDILT C T 51 rs114263339 5 50932343 ISL1 C T 52 rs7175642 15 59450079 MYO1E T G 53 rs138329430 1 174619318 RABGAP1L G A 54 55 rs9814758 3 123062657 ADCY5 T G 56 rs4813224 20 16546846 KIF16B T C 57 rs112859723 3 131625376 CPNE4 T C 58 rs651533 1 82375561 LPHN2 T A 59 rs9425634 1 184663581 EDEM3 T C 60 rs719802 11 113234679 TTC12 T C

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1 2 rs8008772 14 88321884 GALC A T 3 rs56803094 15 99222509 IGF1R A G 4 rs39674 16 9413210 C16orf72 C G 5 rs7928320 11 116942753 SIK3 C G 6 7 rs4419475 4 96150044 UNC5C A T 8 rs555754158 11 46141511 PHF21A G A 9 rs75957461 19 11166163 SMARCA4 C T 10 rs28462076 4 65696174 TECRL A G 11 rs9462670 6 41014309 OARD1 G C 12 Confidential: For Review Only 13 rs66674732 13 62721160 PCDH20 G A 14 rs2542615 10 131128952 MGMT C T 15 rs2083323 18 1856272 METTL4 G A 16 rs4739558 8 38337264 FGFR1 A G 17 rs1017529 17 27912415 GIT1 C A 18 19 rs11218510 11 121922587 BLID G A 20 rs4077093 12 51593616 POU6F1 T G 21 rs559390 20 54157546 CBLN4 A T 22 rs4672338 2 60217457 BCL11A C T 23 rs12692596 2 161265910 RBMS1 C T 24 25 rs8124896 20 21385659 NKX2-4 T C 26 rs6823268 4 145982563 ANAPC10 A G 27 rs10842231 12 23986029 SOX5 A T 28 rs7255223 19 32824310 ZNF507 C A 29 rs6445258 3 62112198 PTPRG T C 30 31 rs1126930 12 49399132 PRKAG1 G C 32 rs17773370 18 57951433 MC4R G A 33 rs12634936 3 147716498 ZIC1 T C 34 rs10835498 11 29258947 KCNA4 G A 35 rs34373881 3 20432033 SGOL1 G A 36 37 rs10115920 9 6926233 KDM4C G A 38 rs59428052 2 53861389 GPR75-ASB3 A G 39 rs9922288 16 24550930 RBBP6 A G 40 rs34778589 22 50709957 MAPK11 A C 41 rs1409158 1 119538890 TBX15 C T 42 43 rs4660586 1 42407229 HIVEP3 C T 44 rs12454712 18 60845884 BCL2 T C 45 rs12037905 1 219628036 SLC30A10 C T 46 rs9291822 5 64076515 CWC27 C T 47 rs2135745 9 109150784 ZNF462 C G 48 49 rs10774018 12 2157925 CACNA1C G C 50 rs2333607 14 30078920 PRKD1 A C 51 rs7141912 14 35649431 KIAA0391 A T 52 rs1987960 20 30649834 HCK T C 53 rs1964926 21 42653121 BACE2 A G 54 55 rs10779835 1 230299949 GALNT2 T C 56 rs4663213 2 236807893 AGAP1 G A 57 rs827803 3 157920266 RSRC1 G T 58 rs10973159 9 36992547 PAX5 G T 59 rs12821416 12 58580570 XRCC6BP1 C T 60 rs2660241 16 4940023 PPL T C

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1 2 rs7570446 2 193801010 TMEFF2 C A 3 rs57590313 4 113323430 ALPK1 C A 4 rs2941432 8 76532219 HNF4G T A 5 rs1547205 9 98815145 ERCC6L2 G C 6 7 rs2658797 11 93212254 SMCO4 C T 8 rs28408562 15 60917079 RORA C G 9 rs6511826 19 12706991 ZNF490 G A 10 rs61986330 14 73314450 DPF3 C A 11 rs8045063 16 49064424 CBLN1 G A 12 Confidential: For Review Only 13 rs9319615 17 79072594 BAIAP2 A C 14 rs8089514 18 69224478 RP11-723G8.2 T A 15 rs11513729 12 112273499 MAPKAPK5 C T 16 rs4677813 3 194863860 XXYLT1 T C 17 rs12705894 7 113351252 PPP1R3A G A 18 19 rs35894137 8 43071838 HGSNAT C T 20 rs10960276 9 11819686 TYRP1 C A 21 rs10823826 10 53649431 PRKG1 C T 22 rs73982435 17 31473455 ASIC2 C T 23 rs1517037 18 56878274 GRP C T 24 25 rs142315514 1 147050816 BCL9 C A 26 rs75706763 2 145669168 ZEB2 A G 27 rs11976084 7 137437156 DGKI C T 28 rs1369159 15 66360842 MEGF11 C T 29 rs12477385 2 166144850 SCN2A G T 30 31 rs72618637 2 48953979 GTF2A1L T A 32 rs1905616 8 93235675 RUNX1T1 G A 33 rs11134512 5 167847460 WWC1 T G 34 rs142503704 5 92622421 NR2F1 G A 35 rs9529148 13 67419495 PCDH9 G A 36 37 rs11708540 3 70593081 FOXP1 G A 38 rs62379271 5 105870033 EFNA5 T G 39 rs1324110 6 93913200 EPHA7 G C 40 rs2450444 10 93010383 PCGF5 G A 41 rs7913496 10 10257277 CELF2 C T 42 43 rs6069625 20 54747469 MC3R A G 44 rs1633418 22 20091756 DGCR8 T C 45 rs11208659 1 65979280 LEPR T C 46 rs11642387 16 6753239 RBFOX1 A G 47 rs4432271 16 20245283 GP2 C T 48 49 rs368540015 7 74292165 GTF2IRD2 A G 50 rs17619860 8 87779603 CNGB3 T C 51 rs1296685 22 18230964 BID A G 52 rs4307239 7 24354300 NPY A G 53 rs1977658 1 107607037 PRMT6 T G 54 55 rs12644329 4 143634746 INPP4B G A 56 rs1865341 9 8845911 PTPRD C T 57 rs1834144 18 40744790 RIT2 C A 58 rs537508 4 171042158 AADAT G C 59 rs10457469 6 126083658 HEY2 G A 60 rs6950388 7 1270699 UNCX G A

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1 2 rs28465175 15 53427155 ONECUT1 A G 3 rs12971645 19 45807945 MARK4 G A 4 rs4908677 1 7738180 CAMTA1 C T 5 rs4425224 3 56249398 ERC2 C A 6 7 rs35775580 7 130420740 KLF14 A G 8 rs3125326 10 63053788 TMEM26 A C 9 rs868784 11 43944388 C11orf96 G A 10 rs7518221 1 225561346 DNAH14 T C 11 rs72851476 2 142874787 LRP1B A C 12 Confidential: For Review Only 13 rs2417998 9 111958746 EPB41L4B C G 14 rs12363672 11 55684028 OR5W2 A C 15 rs680071 11 103088414 DYNC2H1 T C 16 rs61754230 12 72179446 RAB21 C T 17 rs34542489 17 51917844 KIF2B A C 18 19 rs12630209 3 156881392 CCNL1 T G 20 rs1381010 4 112677085 C4orf32 G A 21 rs2076363 1 6684906 THAP3 C G 22 rs1799507 12 16427314 SLC15A5 G A 23 rs6029180 20 39178923 MAFB A G 24 25 rs7511698 1 25015638 SRRM1 C T 26 rs1229984 4 100239319 ADH1B T C 27 rs8111074 19 51776117 SIGLECL1 G T 28 rs10169594 2 41637688 C2orf91 T C 29 rs113079574 4 147354089 SLC10A7 C T 30 31 rs115778101 1 78198554 USP33 T C 32 rs3823674 7 50571996 DDC C T 33 rs35221880 12 133301500 ANKLE2 T C 34 rs2576135 13 54691442 OLFM4 T A 35 rs4989244 9 102100348 SEC61B G A 36 37 rs7020196 9 12289527 TYRP1 C T 38 rs1899689 7 121964349 CADPS2 C T 39 rs9615723 22 48386670 FAM19A5 C T 40 rs557951 3 62713263 CADPS T G 41 rs2736154 6 31706850 CLIC1 A T 42 43 rs8134638 21 40644170 BRWD1 T C 44 rs630602 1 54728864 SSBP3 G C 45 rs4266606 8 28043673 ELP3 C T 46 rs12376870 9 117890567 TNC G A 47 rs12885251 14 99670791 BCL11B G A 48 49 rs57654548 3 125196904 SNX4 C A 50 rs2164300 4 67813017 CENPC C T 51 rs1851823 7 109218983 FLJ00325 C A 52 rs2744801 1 41155486 NFYC C T 53 rs12681792 8 62054463 CLVS1 C A 54 55 rs7086898 10 104386152 SUFU A G 56 rs4500770 16 74658430 RFWD3 A T 57 rs4545921 19 49646006 PPFIA3 A G 58 rs148137538 1 173399677 PRDX6 A G 59 rs74929176 17 54905494 C17orf67 C T 60 rs9888533 13 107854612 FAM155A C T

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1 2 rs535487752 17 73848542 WBP2 T A 3 rs7539903 1 209208033 CAMK1G T A 4 rs36023504 4 38698924 KLF3 C T 5 rs11765062 7 54417515 VSTM2A T C 6 7 rs143662847 8 48804722 PRKDC C T 8 rs10160769 11 76474827 TSKU G C 9 rs6416134 11 45352781 SYT13 G C 10 rs2247401 15 53156672 ONECUT1 G A 11 rs35390852 4 143067054 INPP4B G A 12 Confidential: For Review Only 13 rs71500718 8 15434456 TUSC3 G C 14 rs111584879 15 66678173 TIPIN T C 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 3: Genome-wide association study results for adulthood2 body size in the UK Biobank SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequency Beta Standard Error P 7 0.595371 -0.04652 0.00139707 4.00E-243 8 0.766902 -0.03519 0.00162237 2.60E-104 9 0.171957 -0.03645 0.00182023 3.20E-89 10 0.795046 -0.03016 0.00169526 8.40E-71 11 12 Confidential:0.966108 0.063577 0.00389441 For Review6.50E-60 Only 13 0.513963 -0.02002 0.00136857 1.80E-48 14 0.811547 0.024542 0.00175291 1.50E-44 15 0.827755 -0.02528 0.00181803 5.70E-44 16 0.565253 -0.01867 0.00138436 1.80E-41 17 18 0.615537 -0.01862 0.00141036 8.40E-40 19 0.488186 -0.01755 0.00137056 1.50E-37 20 0.600456 -0.01728 0.00140127 5.90E-35 21 0.805697 0.020764 0.00173237 4.20E-33 22 23 0.604907 0.016755 0.00140266 6.90E-33 24 0.328032 0.017384 0.00145749 8.50E-33 25 0.87821 -0.0247 0.00211727 1.90E-31 26 0.774304 0.018451 0.0016375 1.90E-29 27 0.92511 -0.02871 0.00260568 3.10E-28 28 29 0.591453 -0.01503 0.00139188 3.40E-27 30 0.324953 -0.01579 0.00146479 4.10E-27 31 0.517555 -0.01476 0.00137637 8.10E-27 32 0.808963 0.01857 0.00173761 1.20E-26 33 0.677521 -0.01552 0.00146443 3.10E-26 34 35 0.659718 -0.01502 0.00144491 2.70E-25 36 0.185088 -0.01831 0.00176638 3.50E-25 37 0.590358 0.014399 0.0013964 6.20E-25 38 0.688473 -0.01524 0.00149355 1.80E-24 39 0.76914 0.016596 0.00162688 2.00E-24 40 41 0.398085 0.014201 0.0014016 4.00E-24 42 0.622254 0.01431 0.00141495 4.80E-24 43 0.386749 -0.01426 0.00141252 5.90E-24 44 0.428913 -0.01447 0.00143954 9.10E-24 45 0.68029 -0.01462 0.00146919 2.60E-23 46 47 0.916171 0.024702 0.00248459 2.70E-23 48 0.862972 -0.01994 0.00200994 3.50E-23 49 0.974003 -0.04278 0.00431814 3.90E-23 50 0.870646 -0.02003 0.00206205 2.60E-22 51 0.778004 -0.016 0.00165074 3.20E-22 52 53 0.448702 0.01317 0.00138617 2.10E-21 54 0.795594 0.016236 0.00171408 2.70E-21 55 0.68227 0.013795 0.00147616 9.20E-21 56 0.363991 -0.01332 0.00142984 1.20E-20 57 0.505066 0.01274 0.00137473 1.90E-20 58 59 0.678022 -0.01361 0.00146958 2.00E-20 60 0.912739 0.022832 0.00248522 4.00E-20 0.491242 0.013257 0.00144434 4.40E-20

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1 2 0.425673 0.012679 0.00139004 7.40E-20 3 0.187649 0.016523 0.00182279 1.30E-19 4 0.566335 0.012536 0.00138627 1.50E-19 5 0.864324 -0.0183 0.00202748 1.80E-19 6 7 0.540271 -0.01243 0.00138188 2.30E-19 8 0.360457 0.012819 0.00142617 2.50E-19 9 0.8077 0.015693 0.00174901 2.90E-19 10 0.484614 0.012283 0.00136952 3.00E-19 11 0.545301 0.012393 0.00138267 3.20E-19 12 Confidential: For Review Only 13 0.905761 0.021447 0.00240105 4.20E-19 14 0.534535 0.012293 0.00137833 4.70E-19 15 0.660603 0.012887 0.00145125 6.70E-19 16 0.462687 -0.01218 0.00138306 1.30E-18 17 0.442815 -0.01219 0.00138837 1.60E-18 18 19 0.859126 0.017414 0.00199799 2.90E-18 20 0.75258 0.013787 0.00159576 5.60E-18 21 0.323165 -0.01265 0.00146766 6.90E-18 22 0.846299 0.016329 0.00191052 1.30E-17 23 0.438452 -0.01174 0.00137839 1.60E-17 24 25 0.440914 0.011738 0.00138729 2.60E-17 26 0.465195 0.011697 0.00138218 2.60E-17 27 0.845733 0.016069 0.00190178 2.90E-17 28 0.398676 -0.01181 0.00140063 3.50E-17 29 0.48458 0.01157 0.00137389 3.70E-17 30 31 0.3153 -0.0124 0.00147968 5.20E-17 32 0.44279 -0.01164 0.00138966 5.40E-17 33 0.671402 0.012234 0.00146379 6.40E-17 34 0.409353 -0.01156 0.00138957 9.10E-17 35 0.318742 0.012253 0.00147912 1.20E-16 36 37 0.78596 0.013797 0.00167313 1.60E-16 38 0.423716 0.011422 0.00138666 1.80E-16 39 0.485411 -0.01138 0.00138238 1.90E-16 40 0.364264 -0.01176 0.00143024 2.00E-16 41 0.82989 0.015032 0.00182987 2.10E-16 42 43 0.632865 0.011779 0.00143412 2.10E-16 44 0.51076 -0.01123 0.00137268 2.90E-16 45 0.79024 -0.01376 0.00168297 3.00E-16 46 0.674209 0.011935 0.00146505 3.80E-16 47 0.739445 0.012616 0.00157671 1.20E-15 48 49 0.404079 -0.01135 0.00142746 1.90E-15 50 0.34231 0.01146 0.00144519 2.20E-15 51 0.637766 0.011231 0.00142704 3.50E-15 52 0.584018 0.010961 0.00139251 3.50E-15 53 0.405272 -0.01103 0.00140599 4.40E-15 54 55 0.80983 0.013851 0.00176589 4.40E-15 56 0.5748 -0.01092 0.00139455 4.80E-15 57 0.527217 -0.0107 0.00137118 5.90E-15 58 0.67034 -0.01148 0.00146997 5.90E-15 59 0.436787 0.010754 0.00137834 6.10E-15 60 0.885558 0.016759 0.00215398 7.20E-15

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1 2 0.711353 -0.0117 0.00150889 8.70E-15 3 0.898985 0.017741 0.00229148 9.80E-15 4 0.417338 0.010685 0.0013873 1.30E-14 5 0.704732 0.011615 0.00150727 1.30E-14 6 7 0.553292 0.010598 0.00137933 1.50E-14 8 0.581219 0.010788 0.00140507 1.60E-14 9 0.736665 0.012019 0.0015664 1.70E-14 10 0.437549 0.010556 0.00138011 2.00E-14 11 0.780037 0.012759 0.00167171 2.30E-14 12 Confidential: For Review Only 13 0.72828 -0.01181 0.00154676 2.30E-14 14 0.519459 -0.01047 0.00137409 2.60E-14 15 0.959739 0.026372 0.0034926 4.30E-14 16 0.384832 -0.01089 0.0014426 4.30E-14 17 0.589752 0.010467 0.00138822 4.70E-14 18 19 0.647257 0.010795 0.00143318 5.00E-14 20 0.831 0.013732 0.00182503 5.30E-14 21 0.810445 -0.01321 0.00175805 5.70E-14 22 0.47215 -0.01031 0.00137304 5.80E-14 23 0.88505 0.016218 0.00216124 6.20E-14 24 25 0.917922 -0.01875 0.00250189 6.70E-14 26 0.373748 -0.01056 0.00141638 9.00E-14 27 0.492239 0.010244 0.00137406 9.00E-14 28 0.858841 0.014638 0.00197063 1.10E-13 29 0.773735 0.012152 0.00163666 1.10E-13 30 31 0.702696 0.011151 0.00150201 1.10E-13 32 0.166309 0.013642 0.00183985 1.20E-13 33 0.636705 0.010592 0.00142731 1.20E-13 34 0.6123 0.010449 0.00141098 1.30E-13 35 0.767269 -0.01207 0.00162981 1.30E-13 36 37 0.845759 0.014068 0.00190031 1.30E-13 38 0.388097 0.010434 0.00141137 1.40E-13 39 0.621245 0.010479 0.00141618 1.40E-13 40 0.539336 0.010253 0.00138891 1.60E-13 41 0.210923 -0.01236 0.00167752 1.80E-13 42 43 0.444505 0.010243 0.00139113 1.80E-13 44 0.839148 0.013771 0.00186963 1.80E-13 45 0.786103 -0.01228 0.00166938 1.90E-13 46 0.0770298 0.018863 0.00257351 2.30E-13 47 0.944091 -0.02215 0.00302303 2.30E-13 48 49 0.718219 -0.01121 0.00153204 2.50E-13 50 0.63894 0.01047 0.00143054 2.50E-13 51 0.704403 -0.011 0.00150528 2.70E-13 52 0.618149 -0.01051 0.0014385 2.80E-13 53 0.577896 -0.01013 0.00139037 3.10E-13 54 55 0.268201 -0.01131 0.00155186 3.20E-13 56 0.890178 0.015905 0.00219022 3.80E-13 57 0.317602 0.010739 0.00148333 4.50E-13 58 0.571866 -0.00997 0.00138657 6.60E-13 59 0.745081 -0.01132 0.00157548 6.60E-13 60 0.756236 -0.0115 0.00160241 7.30E-13

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1 2 0.322314 0.010504 0.00146427 7.30E-13 3 0.714944 0.010937 0.00152786 8.20E-13 4 0.756352 0.011415 0.00159677 8.70E-13 5 0.51337 -0.00987 0.00138141 9.20E-13 6 7 0.50706 -0.00978 0.00137366 1.10E-12 8 0.57862 0.009936 0.0013964 1.10E-12 9 0.5316 0.009861 0.00138545 1.10E-12 10 0.533103 0.009801 0.00137971 1.20E-12 11 0.726343 -0.01097 0.00154606 1.30E-12 12 Confidential: For Review Only 13 0.633959 0.0101 0.00142485 1.40E-12 14 0.725853 -0.01109 0.00156809 1.50E-12 15 0.771778 0.011564 0.00163545 1.50E-12 16 0.812733 -0.01256 0.00177792 1.60E-12 17 0.17938 0.012636 0.00179146 1.70E-12 18 19 0.77558 -0.01159 0.00164338 1.80E-12 20 0.611666 -0.00995 0.00141493 2.00E-12 21 0.813835 -0.01244 0.00176815 2.00E-12 22 0.864423 -0.01465 0.00208415 2.10E-12 23 0.49667 0.009634 0.00137162 2.20E-12 24 25 0.552223 -0.00969 0.00138007 2.20E-12 26 0.851925 -0.01362 0.00194393 2.40E-12 27 0.84206 0.01337 0.00191182 2.70E-12 28 0.334299 -0.01018 0.00145748 2.90E-12 29 0.526852 0.009657 0.00138429 3.00E-12 30 31 0.417165 -0.00966 0.00138887 3.50E-12 32 0.637787 -0.00991 0.00142688 3.80E-12 33 0.692223 0.01031 0.00148708 4.10E-12 34 0.75472 0.011047 0.00159322 4.10E-12 35 0.60427 0.009759 0.00140786 4.10E-12 36 37 0.590818 -0.00965 0.00139325 4.30E-12 38 0.617867 0.009803 0.0014192 4.90E-12 39 0.522565 0.009517 0.00137849 5.10E-12 40 0.853006 -0.01335 0.00193619 5.30E-12 41 0.862284 0.013712 0.00199026 5.60E-12 42 43 0.435427 0.009549 0.00138642 5.70E-12 44 0.916465 -0.01707 0.00247827 5.70E-12 45 0.507904 0.00988 0.00143461 5.70E-12 46 0.757091 -0.01104 0.00160426 6.00E-12 47 0.708687 -0.01044 0.00152144 6.80E-12 48 49 0.166193 0.012582 0.00183897 7.80E-12 50 0.838208 0.012723 0.00185993 7.90E-12 51 0.284406 0.010398 0.0015204 8.00E-12 52 0.77991 0.011476 0.00167813 8.00E-12 53 0.867546 -0.01386 0.00202875 8.30E-12 54 55 0.844199 -0.01293 0.00189361 8.50E-12 56 0.580515 0.009488 0.00139007 8.80E-12 57 0.757298 0.01091 0.00159892 8.90E-12 58 0.458691 -0.00939 0.00137682 9.00E-12 59 0.636608 0.009739 0.00143449 1.10E-11 60 0.616385 -0.00972 0.00143319 1.20E-11

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1 2 0.664094 -0.00986 0.00145393 1.20E-11 3 0.697835 -0.01014 0.0014973 1.20E-11 4 0.0325877 -0.02642 0.00389465 1.20E-11 5 0.1622 0.012581 0.00185776 1.30E-11 6 7 0.511511 -0.00929 0.00137304 1.30E-11 8 0.588642 -0.00948 0.00140121 1.40E-11 9 0.60699 -0.00952 0.00141154 1.50E-11 10 0.826017 -0.01226 0.00182095 1.60E-11 11 0.427582 0.00931 0.00138359 1.70E-11 12 Confidential: For Review Only 13 0.590095 0.009348 0.00139222 1.90E-11 14 0.303859 0.010038 0.0014969 2.00E-11 15 0.965963 0.02668 0.00397873 2.00E-11 16 0.703219 0.010595 0.00158158 2.10E-11 17 0.941951 0.019718 0.00294476 2.10E-11 18 19 0.356054 0.009624 0.00143716 2.10E-11 20 0.72369 0.010397 0.0015534 2.20E-11 21 0.446551 0.009236 0.00138226 2.40E-11 22 0.739061 -0.01044 0.00156447 2.50E-11 23 0.678317 -0.00979 0.00146872 2.60E-11 24 25 0.415805 -0.00928 0.00139315 2.70E-11 26 0.88671 0.014349 0.00215753 2.90E-11 27 0.382148 -0.00946 0.00142256 2.90E-11 28 0.716165 -0.01013 0.00152324 3.00E-11 29 0.876132 -0.01381 0.00207909 3.10E-11 30 31 0.84213 0.012651 0.00190443 3.10E-11 32 0.471527 -0.00914 0.00137713 3.20E-11 33 0.319388 0.009748 0.00147061 3.40E-11 34 0.316129 0.009806 0.00148041 3.50E-11 35 0.706341 -0.00998 0.00150851 3.70E-11 36 37 0.945907 -0.02019 0.00305238 3.80E-11 38 0.200937 0.011348 0.00171932 4.10E-11 39 0.864006 -0.01325 0.00201085 4.30E-11 40 0.274935 -0.01027 0.00156368 5.10E-11 41 0.587612 -0.00916 0.00139468 5.10E-11 42 43 0.969118 0.025959 0.00396473 5.90E-11 44 0.724364 -0.01006 0.00153629 5.90E-11 45 0.695664 0.009758 0.00149027 5.90E-11 46 0.931102 -0.01775 0.00271192 5.90E-11 47 0.945453 0.019936 0.00304655 6.00E-11 48 49 0.603989 -0.00917 0.00140267 6.30E-11 50 0.91859 -0.01768 0.0027129 7.20E-11 51 0.938199 0.018501 0.00284688 8.10E-11 52 0.814306 0.011462 0.00176411 8.20E-11 53 0.925586 -0.01711 0.00263645 8.60E-11 54 55 0.904445 -0.01513 0.00233311 8.90E-11 56 0.686634 0.009594 0.00147977 9.00E-11 57 0.900098 0.01518 0.00234294 9.20E-11 58 0.678103 -0.01019 0.00157523 9.80E-11 59 0.731353 0.010046 0.00155554 1.10E-10 60 0.846977 -0.01233 0.0019113 1.10E-10

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1 2 0.762853 -0.01052 0.00163159 1.10E-10 3 0.658268 0.009346 0.00145015 1.20E-10 4 0.614657 -0.00913 0.0014182 1.20E-10 5 0.903818 -0.01497 0.00232404 1.20E-10 6 7 0.664927 0.009318 0.00145169 1.40E-10 8 0.902215 0.014829 0.00231302 1.40E-10 9 0.71933 0.009995 0.00156387 1.60E-10 10 0.657996 -0.00922 0.00144166 1.60E-10 11 0.291024 0.009634 0.00150661 1.60E-10 12 Confidential: For Review Only 13 0.661365 0.009261 0.00144711 1.60E-10 14 0.196058 -0.01109 0.00173557 1.70E-10 15 0.527662 -0.00889 0.00139474 1.80E-10 16 0.456461 0.00878 0.0013771 1.80E-10 17 0.660972 0.009228 0.00144668 1.80E-10 18 19 0.492297 -0.00872 0.00137121 2.00E-10 20 0.268921 -0.00987 0.00155197 2.00E-10 21 0.777099 -0.01061 0.00166847 2.00E-10 22 0.812371 -0.01114 0.00175359 2.10E-10 23 0.353154 0.009119 0.00143655 2.20E-10 24 25 0.561245 -0.00878 0.0013839 2.20E-10 26 0.601042 -0.00892 0.00140514 2.20E-10 27 0.411293 -0.00884 0.00139518 2.40E-10 28 0.88381 -0.01357 0.00214705 2.60E-10 29 0.549911 0.008737 0.00138531 2.80E-10 30 31 0.794869 0.010794 0.00171155 2.90E-10 32 0.637079 -0.00896 0.00142305 3.00E-10 33 0.565776 -0.00874 0.00138674 3.00E-10 34 0.90585 -0.01517 0.00241102 3.10E-10 35 0.744433 0.009925 0.001578 3.20E-10 36 37 0.770897 -0.01051 0.00167201 3.30E-10 38 0.893101 -0.01402 0.00223036 3.30E-10 39 0.348838 0.009019 0.00143697 3.50E-10 40 0.910471 -0.01514 0.00241294 3.50E-10 41 0.574127 -0.00873 0.00139086 3.50E-10 42 43 0.614902 -0.00887 0.00141365 3.60E-10 44 0.854953 -0.0126 0.00200967 3.60E-10 45 0.741579 -0.00985 0.00157289 3.70E-10 46 0.835791 -0.01162 0.00185594 3.80E-10 47 0.156158 -0.01183 0.00188917 3.80E-10 48 49 0.346246 0.009074 0.00145054 4.00E-10 50 0.705419 0.009397 0.00150477 4.20E-10 51 0.227587 0.010183 0.00163239 4.40E-10 52 0.462891 -0.00864 0.00138424 4.40E-10 53 0.830859 -0.01149 0.00184196 4.50E-10 54 55 0.873489 0.012927 0.00207355 4.50E-10 56 0.493942 -0.00857 0.00137526 4.60E-10 57 0.573589 -0.00867 0.00139549 5.20E-10 58 0.77093 0.010113 0.0016282 5.30E-10 59 0.660807 -0.00897 0.00144403 5.30E-10 60 0.330577 -0.00909 0.00146502 5.50E-10

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1 2 0.114454 -0.01331 0.00215072 6.00E-10 3 0.592379 -0.00864 0.00139769 6.20E-10 4 0.35571 0.00883 0.00142922 6.50E-10 5 0.64299 0.008831 0.00143031 6.70E-10 6 7 0.530781 0.008489 0.00137576 6.80E-10 8 0.606447 0.008672 0.00140574 6.90E-10 9 0.251739 -0.00981 0.00159143 7.20E-10 10 0.969354 0.024563 0.00399409 7.80E-10 11 0.856201 0.011993 0.00195352 8.30E-10 12 Confidential: For Review Only 13 0.918866 0.015592 0.0025405 8.40E-10 14 0.613852 0.008673 0.00141298 8.40E-10 15 0.325079 -0.009 0.00146728 8.40E-10 16 0.509017 -0.00849 0.0013848 8.70E-10 17 0.859392 -0.01206 0.00196697 8.80E-10 18 19 0.9663 0.024017 0.00391789 8.80E-10 20 0.845581 0.012393 0.00202306 9.00E-10 21 0.692539 -0.00908 0.00148344 9.40E-10 22 0.674753 -0.00895 0.00146561 1.00E-09 23 0.979654 -0.0299 0.00489434 1.00E-09 24 25 0.405167 -0.00854 0.00139856 1.00E-09 26 0.942508 -0.01803 0.00295173 1.00E-09 27 0.70965 -0.00967 0.00158251 1.00E-09 28 0.492178 -0.00869 0.00142487 1.10E-09 29 0.683257 -0.00896 0.00146997 1.10E-09 30 31 0.551499 0.008398 0.00137905 1.10E-09 32 0.976639 -0.02882 0.00473238 1.10E-09 33 0.139921 -0.01214 0.00199185 1.10E-09 34 0.444163 0.008422 0.00138117 1.10E-09 35 0.687506 -0.00908 0.00149355 1.20E-09 36 37 0.728811 0.009449 0.00155587 1.30E-09 38 0.89762 -0.01369 0.00225826 1.30E-09 39 0.909819 -0.0147 0.00242091 1.30E-09 40 0.87952 -0.01289 0.00212463 1.30E-09 41 0.602596 -0.00853 0.00140699 1.30E-09 42 43 0.942445 -0.01787 0.00294699 1.30E-09 44 0.9386 -0.01775 0.00293025 1.40E-09 45 0.86542 0.012159 0.0020083 1.40E-09 46 0.894058 -0.01356 0.00224169 1.40E-09 47 0.526114 0.008312 0.00137495 1.50E-09 48 49 0.808023 0.010571 0.00174913 1.50E-09 50 0.384293 -0.00849 0.0014077 1.60E-09 51 0.830398 0.011097 0.0018398 1.60E-09 52 0.815366 0.010772 0.00178542 1.60E-09 53 0.59595 0.008683 0.00144114 1.70E-09 54 55 0.753648 -0.0099 0.00164361 1.70E-09 56 0.958742 0.022662 0.00376431 1.70E-09 57 0.772109 0.00991 0.00164497 1.70E-09 58 0.508934 -0.0083 0.00137898 1.70E-09 59 0.64772 0.008631 0.00143586 1.80E-09 60 0.680028 0.008848 0.00147397 1.90E-09

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1 2 0.322821 0.008814 0.00146753 1.90E-09 3 0.966576 -0.02322 0.00386698 1.90E-09 4 0.946891 0.018479 0.00307566 1.90E-09 5 0.789394 0.010137 0.001689 2.00E-09 6 7 0.626845 -0.00848 0.00141586 2.10E-09 8 0.754126 0.009517 0.00158929 2.10E-09 9 0.714677 0.009142 0.00152583 2.10E-09 10 0.928673 -0.01653 0.00275855 2.10E-09 11 0.331743 0.008789 0.00147166 2.30E-09 12 Confidential: For Review Only 13 0.414559 -0.00832 0.00139678 2.60E-09 14 0.689843 0.00886 0.00148784 2.60E-09 15 0.115109 0.012853 0.0021599 2.70E-09 16 0.196434 -0.01028 0.0017268 2.70E-09 17 0.948091 -0.01876 0.00315301 2.70E-09 18 19 0.672805 -0.00873 0.00146694 2.70E-09 20 0.565455 -0.00825 0.00138786 2.80E-09 21 0.410365 0.00828 0.00139468 2.90E-09 22 0.509694 -0.00836 0.00141129 3.10E-09 23 0.367968 0.008444 0.0014248 3.10E-09 24 25 0.709906 -0.00901 0.00152109 3.20E-09 26 0.782638 0.009952 0.00168107 3.20E-09 27 0.92234 -0.01509 0.00255465 3.40E-09 28 0.732386 0.00918 0.00155262 3.40E-09 29 0.44315 0.008172 0.00138361 3.50E-09 30 31 0.973181 0.025063 0.00424894 3.70E-09 32 0.671468 0.009045 0.00153465 3.80E-09 33 0.960851 -0.02132 0.00361813 3.80E-09 34 0.985349 -0.03439 0.00584937 4.10E-09 35 0.543763 -0.00815 0.00138623 4.10E-09 36 37 0.608886 -0.00835 0.00142292 4.30E-09 38 0.212936 0.009884 0.00168301 4.30E-09 39 0.756637 -0.00939 0.00160014 4.40E-09 40 0.364025 -0.00833 0.00142051 4.50E-09 41 0.850588 -0.01126 0.00192094 4.60E-09 42 43 0.206723 0.010246 0.00174849 4.60E-09 44 0.703431 0.008806 0.00150452 4.80E-09 45 0.437907 -0.00811 0.0013842 4.80E-09 46 0.595776 -0.0082 0.00140095 4.80E-09 47 0.964436 -0.02189 0.00374062 4.90E-09 48 49 0.789213 -0.00986 0.00168442 4.90E-09 50 0.714076 -0.00886 0.00151546 5.10E-09 51 0.974247 -0.02528 0.00432869 5.20E-09 52 0.341586 0.008591 0.00147129 5.20E-09 53 0.890239 -0.0128 0.00219309 5.40E-09 54 55 0.6439 0.008387 0.00143726 5.40E-09 56 0.262182 -0.00912 0.0015635 5.40E-09 57 0.842887 0.011143 0.00191128 5.50E-09 58 0.243821 0.009296 0.00159479 5.60E-09 59 0.541865 -0.00799 0.00137157 5.70E-09 60 0.385578 0.0082 0.0014076 5.70E-09

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1 2 0.749476 -0.00926 0.00159022 5.70E-09 3 0.773245 0.009577 0.00164509 5.80E-09 4 0.30395 -0.00871 0.00149816 6.00E-09 5 0.943461 -0.01729 0.00297269 6.10E-09 6 7 0.59261 -0.0081 0.00139493 6.50E-09 8 0.987473 -0.0387 0.00666806 6.50E-09 9 0.945909 -0.01768 0.00304742 6.60E-09 10 0.761729 0.009393 0.00162009 6.70E-09 11 0.769356 -0.00942 0.00162679 7.10E-09 12 Confidential: For Review Only 13 0.61748 -0.00816 0.00141088 7.20E-09 14 0.342139 0.008436 0.00145857 7.30E-09 15 0.822294 -0.01041 0.00179988 7.30E-09 16 0.399483 0.008097 0.00140056 7.40E-09 17 0.825162 -0.01062 0.00183966 7.70E-09 18 19 0.599589 0.008096 0.00140221 7.80E-09 20 0.215777 0.009691 0.00167974 7.90E-09 21 0.658242 -0.00837 0.00145118 7.90E-09 22 0.663755 -0.00835 0.00144845 8.00E-09 23 0.628118 -0.00816 0.00141428 8.10E-09 24 25 0.899001 -0.01317 0.00228357 8.10E-09 26 0.628532 -0.00818 0.00141821 8.20E-09 27 0.916952 -0.01443 0.00250521 8.40E-09 28 0.735259 0.008967 0.00155716 8.50E-09 29 0.207559 0.009711 0.00168697 8.60E-09 30 31 0.964697 -0.02138 0.0037155 8.60E-09 32 0.933966 -0.01589 0.00276123 8.70E-09 33 0.943292 -0.0181 0.00314699 8.80E-09 34 0.5691 -0.00798 0.00138744 8.90E-09 35 0.724699 0.008833 0.00153671 9.00E-09 36 37 0.348576 -0.00829 0.00144216 9.00E-09 38 0.851083 0.011466 0.00199987 9.80E-09 39 0.235517 0.009389 0.00163749 9.80E-09 40 0.916868 -0.01434 0.0025 9.80E-09 41 0.237368 0.009231 0.00161087 1.00E-08 42 43 0.260631 0.008961 0.00156363 1.00E-08 44 0.623174 -0.00811 0.00141626 1.00E-08 45 0.580639 0.007927 0.00138814 1.10E-08 46 0.485041 0.007904 0.00138376 1.10E-08 47 0.2485 0.009128 0.00159545 1.10E-08 48 49 0.779662 -0.00948 0.00165987 1.10E-08 50 0.380725 0.00817 0.0014303 1.10E-08 51 0.873721 0.011821 0.00206846 1.10E-08 52 0.0475408 -0.01893 0.00331178 1.10E-08 53 0.354052 -0.00823 0.00143981 1.10E-08 54 55 0.387126 0.00801 0.00140611 1.20E-08 56 0.221788 0.009461 0.00165947 1.20E-08 57 0.434419 0.007866 0.00138053 1.20E-08 58 0.379951 -0.00805 0.00141346 1.20E-08 59 0.864002 -0.01139 0.0019995 1.20E-08 60 0.635152 -0.00813 0.00142623 1.20E-08

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1 2 0.455515 -0.0078 0.00137254 1.30E-08 3 0.80729 -0.01017 0.00178824 1.30E-08 4 0.527512 -0.00801 0.0014092 1.30E-08 5 0.900067 0.013205 0.00232169 1.30E-08 6 7 0.517623 0.007791 0.00137105 1.30E-08 8 0.553002 -0.00784 0.00137968 1.30E-08 9 0.0868843 0.013982 0.00245639 1.30E-08 10 0.725696 0.008733 0.00153905 1.40E-08 11 0.810292 -0.00998 0.00176025 1.40E-08 12 Confidential: For Review Only 13 0.446918 0.007836 0.00138103 1.40E-08 14 0.631443 -0.00817 0.00143938 1.40E-08 15 0.58693 0.007993 0.00141154 1.50E-08 16 0.750189 0.008933 0.00158099 1.60E-08 17 0.447911 0.007801 0.00138156 1.60E-08 18 19 0.919131 0.014227 0.00251993 1.60E-08 20 0.644607 0.008094 0.00143164 1.60E-08 21 0.751302 -0.00898 0.00158888 1.60E-08 22 0.784163 0.009429 0.00166802 1.60E-08 23 0.811867 0.009923 0.00175754 1.60E-08 24 25 0.964594 -0.02139 0.00379002 1.70E-08 26 0.948316 -0.0177 0.00313665 1.70E-08 27 0.712454 -0.00857 0.00151882 1.70E-08 28 0.420399 0.007875 0.0013963 1.70E-08 29 0.7745 0.009244 0.00164143 1.80E-08 30 31 0.810545 0.009992 0.00177487 1.80E-08 32 0.66871 0.008197 0.00145677 1.80E-08 33 0.676993 0.008242 0.00146708 1.90E-08 34 0.97711 -0.02627 0.00467519 1.90E-08 35 0.377206 -0.008 0.00142353 1.90E-08 36 37 0.84247 -0.01062 0.00189063 2.00E-08 38 0.421389 -0.00781 0.00139152 2.00E-08 39 0.557284 0.00777 0.00138403 2.00E-08 40 0.651052 0.008074 0.00143771 2.00E-08 41 0.179662 0.01003 0.00178629 2.00E-08 42 43 0.726597 0.00873 0.00155672 2.00E-08 44 0.391187 0.007921 0.00141049 2.00E-08 45 0.917081 -0.01392 0.00248512 2.10E-08 46 0.899139 0.012865 0.00229443 2.10E-08 47 0.131408 -0.01156 0.00206349 2.10E-08 48 49 0.929726 -0.01817 0.00324824 2.20E-08 50 0.836864 -0.0104 0.00186001 2.20E-08 51 0.788849 -0.00949 0.00169731 2.20E-08 52 0.541187 -0.00769 0.00137898 2.40E-08 53 0.343121 0.008101 0.00145332 2.50E-08 54 55 0.371783 0.007912 0.00141949 2.50E-08 56 0.238421 -0.009 0.00161509 2.50E-08 57 0.626766 0.00793 0.00142258 2.50E-08 58 0.580943 -0.00777 0.00139636 2.60E-08 59 0.476422 -0.00763 0.00137206 2.60E-08 60 0.204857 -0.00945 0.00169839 2.60E-08

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1 2 0.93018 0.015038 0.00270111 2.60E-08 3 0.724598 0.008594 0.00154345 2.60E-08 4 0.520132 -0.00769 0.00138197 2.70E-08 5 0.105039 0.012442 0.00223714 2.70E-08 6 7 0.953004 0.018015 0.00324057 2.70E-08 8 0.39151 -0.00789 0.00141947 2.70E-08 9 0.619098 0.007872 0.00141664 2.70E-08 10 0.352695 0.007954 0.00143293 2.80E-08 11 0.843679 0.010727 0.00193252 2.80E-08 12 Confidential: For Review Only 13 0.291576 0.008414 0.00151559 2.80E-08 14 0.973835 -0.02384 0.00429171 2.80E-08 15 0.119403 -0.01174 0.0021142 2.80E-08 16 0.980265 -0.02738 0.0049283 2.80E-08 17 0.590246 0.00778 0.00140115 2.80E-08 18 19 0.747146 -0.00875 0.00157875 3.00E-08 20 0.695001 0.008237 0.00148666 3.00E-08 21 0.663112 -0.00803 0.00145135 3.10E-08 22 0.856437 -0.01084 0.00195679 3.10E-08 23 0.673959 -0.00819 0.00147876 3.10E-08 24 25 0.693718 0.00821 0.00148524 3.20E-08 26 0.0271609 -0.02304 0.00416449 3.20E-08 27 0.713638 0.00839 0.00151756 3.20E-08 28 0.636913 -0.00788 0.0014266 3.30E-08 29 0.807329 0.009652 0.0017463 3.30E-08 30 31 0.952035 0.017768 0.00321873 3.40E-08 32 0.572244 0.007657 0.00138882 3.50E-08 33 0.268227 0.008573 0.00155424 3.50E-08 34 0.0929638 0.013167 0.00238721 3.50E-08 35 0.567822 0.007635 0.00138564 3.60E-08 36 37 0.419679 0.007789 0.00141323 3.60E-08 38 0.610356 -0.00774 0.00140509 3.70E-08 39 0.440516 0.007715 0.00140281 3.80E-08 40 0.687123 -0.00814 0.00148083 3.90E-08 41 0.790274 0.010956 0.00199426 3.90E-08 42 43 0.624363 -0.0078 0.00142034 4.00E-08 44 0.393414 -0.00773 0.00140837 4.10E-08 45 0.142631 0.010864 0.0019799 4.10E-08 46 0.762383 0.008866 0.00161573 4.10E-08 47 0.54166 0.007628 0.00139078 4.10E-08 48 49 0.873846 0.011629 0.00212161 4.20E-08 50 0.480766 0.007549 0.00137666 4.20E-08 51 0.511629 -0.00754 0.00137512 4.20E-08 52 0.663446 0.007954 0.00145216 4.30E-08 53 0.807463 -0.00956 0.00174588 4.30E-08 54 55 0.920371 -0.01387 0.00253258 4.30E-08 56 0.637193 0.007821 0.00142756 4.30E-08 57 0.399961 0.007691 0.00140446 4.30E-08 58 0.976551 0.025049 0.00457729 4.40E-08 59 0.773047 0.009047 0.00165261 4.40E-08 60 0.461906 -0.00765 0.00139943 4.50E-08

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1 2 0.83516 -0.01046 0.00191212 4.50E-08 3 0.38457 0.007692 0.00140708 4.60E-08 4 0.617088 0.007774 0.00142237 4.60E-08 5 0.45926 0.007516 0.00137499 4.60E-08 6 7 0.960337 0.019318 0.0035338 4.60E-08 8 0.78263 0.009183 0.00168019 4.60E-08 9 0.181176 -0.00973 0.00178062 4.60E-08 10 0.733175 -0.00852 0.001561 4.70E-08 11 0.876193 -0.01139 0.00208652 4.80E-08 12 Confidential: For Review Only 13 0.480766 -0.00751 0.00137542 4.80E-08 14 0.761347 0.008789 0.00161059 4.80E-08 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 4: Comparison of genome-wide effect estimates between early life and adult body size in the UK Biobank 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs6938973 6 98421721 MMS22L T C 8 rs12042908 1 74997762 TNNI3K A G 9 rs13254613 8 64804804 YTHDF3 A C 10 rs78444298 1 184672098 EDEM3 G A 11 12 rs9843653 Confidential:3 49920571 ForMST1R ReviewT OnlyC 13 rs77960 5 103964585 NUDT12 G A 14 rs4744246 9 96254464 FAM120A A G 15 rs1250597 10 81010250 ZMIZ1 A G 16 rs2725371 8 30854033 PURG A G 17 18 rs1320251 17 21264396 KCNJ12 C T 19 rs7132908 12 50263148 FAIM2 G A 20 rs543874 1 177889480 SEC16B A G 21 rs35957544 8 73440371 KCNB2 G T 22 23 rs788858 4 82138300 PRKG2 A G 24 rs10182458 2 25150641 ADCY3 A G 25 rs115319174 2 207066474 GPR1 G C 26 rs217672 14 62361021 SYT16 A C 27 rs17770336 9 28414625 LINGO2 C T 28 29 rs13292699 9 15910044 CCDC171 A C 30 rs236660 7 75050086 POM121C T C 31 rs429358 19 45411941 APOE T C 32 rs147730268 12 123024476 KNTC1 G T 33 rs2269610 6 33289935 DAXX G C 34 35 rs2999158 1 113239478 MOV10 T C 36 rs4806814 19 1860147 KLF16 G A 37 rs2767486 1 65991203 LEPR A G 38 rs60644673 7 100096742 NYAP1 G T 39 rs34260097 6 100727703 SIM1 T G 40 41 rs72910629 6 69761994 BAI3 A G 42 rs7206608 16 82872628 CDH13 C G 43 rs59227842 11 43692423 HSD17B12 A G 44 rs6265 11 27679916 BDNF C T 45 rs12253527 10 21819824 MLLT10 G A 46 47 rs13186637 5 153108558 GRIA1 T C 48 rs17716502 8 116659731 TRPS1 C T 49 rs12538826 7 99030228 PTCD1 T C 50 rs7424120 2 59313974 FANCL C T 51 rs149457 5 107438057 FBXL17 C T 52 53 rs113569731 3 47093206 SETD2 C A 54 rs62259692 3 51847709 IQCF3 G A 55 rs9421249 10 118623322 ENO4 C T 56 rs1000471 15 89986583 RHCG C T 57 rs181617194 12 122011598 KDM2B T C 58 59 rs6577497 1 8605667 RERE A T 60 rs7424771 2 161276378 RBMS1 G A rs12033257 1 112318484 KCND3 A G

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1 2 rs1840660 7 114352615 FOXP2 G A 3 rs2594994 3 11339960 ATG7 T A 4 rs4077093 12 51593616 POU6F1 T G 5 rs7893571 10 16750129 RSU1 G T 6 7 rs473837 8 60906881 CA8 G T 8 rs11134512 5 167847460 WWC1 T G 9 rs6950388 7 1270699 UNCX G A 10 rs1411432 9 16728532 BNC2 A C 11 rs10960276 9 11819686 TYRP1 C A 12 Confidential: For Review Only 13 rs7570446 2 193801010 TMEFF2 C A 14 rs1454687 3 94038085 NSUN3 C G 15 rs4660586 1 42407229 HIVEP3 C T 16 rs11691869 2 100805996 AFF3 C A 17 rs61971082 13 86494667 SLITRK6 T G 18 19 rs2678204 1 201800511 IPO9 T G 20 rs7548936 1 91207757 BARHL2 G C 21 rs809955 4 140874760 MAML3 G A 22 rs7433076 3 90234502 EPHA3 T A 23 rs13427822 2 213414265 ERBB4 A G 24 25 rs3814883 16 29994922 TAOK2 C T 26 rs2433733 2 230816703 FBXO36 G A 27 rs11642387 16 6753239 RBFOX1 A G 28 rs4658403 1 243832560 AKT3 C T 29 rs11708540 3 70593081 FOXP1 G A 30 31 rs403694 21 46567625 ADARB1 C T 32 rs72976986 19 4050424 ZBTB7A G A 33 rs117911387 9 130446836 STXBP1 G A 34 rs55931203 17 65854602 BPTF C T 35 rs4419475 4 96150044 UNC5C A T 36 37 rs116195355 1 39941508 MACF1 C A 38 rs409696 2 147900651 ACVR2A G A 39 rs73213484 4 28489339 RP11-180C1.1 A T 40 rs10927006 1 243557659 SDCCAG8 T C 41 rs1977658 1 107607037 PRMT6 T G 42 43 rs10499014 6 97947755 MMS22L C G 44 rs2237025 4 55541879 KIT T C 45 rs2164300 4 67813017 CENPC C T 46 rs8192675 3 170724883 SLC2A2 T C 47 rs55880046 16 19941557 GPRC5B T G 48 49 rs11782074 8 142617096 AC138647.1 G T 50 rs9395520 6 13183523 PHACTR1 C T 51 rs601338 19 49206674 FUT2 G A 52 rs12357890 10 99762693 CRTAC1 A G 53 rs117903946 16 67449639 ZDHHC1 G A 54 55 rs62106258 2 417167 FAM150B T C 56 rs8134638 21 40644170 BRWD1 T C 57 rs34517439 1 78450517 DNAJB4 C A 58 rs35852935 4 17991522 LCORL A C 59 rs10973159 9 36992547 PAX5 G T 60 rs4916229 1 171443368 PRRC2C C G

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1 2 rs10774018 12 2157925 CACNA1C G C 3 rs3737992 1 33234128 KIAA1522 G A 4 rs78369934 17 61739101 MAP3K3 T C 5 rs10185199 2 40282202 SLC8A1 G A 6 7 rs10805383 5 63034606 HTR1A G A 8 rs7306710 12 66376091 HMGA2 T C 9 rs6507054 18 31248323 ASXL3 T C 10 rs4572029 10 70889053 VPS26A A G 11 rs34898535 16 31025641 STX1B C T 12 Confidential: For Review Only 13 rs9515446 13 112217108 RP11-65D24.2 A G 14 rs2056477 7 2079744 MAD1L1 G C 15 rs9366863 6 34688946 C6orf106 T C 16 rs1017529 17 27912415 GIT1 C A 17 rs396354 2 86850022 CHMP3 T C 18 19 rs61217499 12 108417780 WSCD2 G C 20 rs151252883 2 228998026 SPHKAP T G 21 rs412243 16 339672 AXIN1 T C 22 rs262956 3 183486117 YEATS2 T G 23 rs71495049 10 34014435 PARD3 G A 24 25 rs3759584 14 103990799 CKB T C 26 rs4425224 3 56249398 ERC2 C A 27 rs2837398 21 41427168 DSCAM A C 28 rs4671328 2 58935282 FANCL T G 29 rs6575340 14 94023972 UNC79 G A 30 31 rs10160769 11 76474827 TSKU G C 32 rs270689 6 104790532 HACE1 A T 33 rs2958542 11 62181882 SCGB1A1 C T 34 rs28726372 1 84353839 TTLL7 T C 35 rs7601895 2 55281901 RTN4 C G 36 37 rs9477762 6 18507853 RNF144B A T 38 rs112898427 2 67561335 ETAA1 C T 39 rs10503555 8 15763818 TUSC3 A G 40 rs28408562 15 60917079 RORA C G 41 rs8011566 14 42939471 LRFN5 T A 42 43 rs7321285 13 54319327 OLFM4 A C 44 rs7958241 12 49509262 LMBR1L A G 45 rs11079849 17 47090785 IGF2BP1 C T 46 rs13104584 4 80811227 ANTXR2 G A 47 rs10169594 2 41637688 C2orf91 T C 48 49 rs58351927 17 5297038 NUP88 A G 50 rs824207 15 24007729 NDN A G 51 rs183315407 1 46201427 IPP G A 52 rs2516726 16 2095065 NTHL1 T C 53 rs1458156 12 41887940 PDZRN4 C T 54 55 rs862320 16 69651866 NFAT5 C T 56 rs10404726 19 18834514 CRTC1 C T 57 rs80236973 3 188001014 LPP C T 58 rs12681792 8 62054463 CLVS1 C A 59 rs67679818 7 110672704 IMMP2L C T 60 rs10204994 2 35443726 CRIM1 G A

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1 2 rs35918296 8 76862208 HNF4G C T 3 rs112380819 3 9498519 SETD5 G A 4 rs567230078 6 43588227 GTPBP2 T A 5 rs1631026 2 26953850 KCNK3 C T 6 7 rs61813324 1 156049877 MEX3A C T 8 rs7084503 10 2666859 PFKP T C 9 rs10174253 2 181323160 CWC22 A C 10 rs1477290 5 87988934 MEF2C T C 11 rs36007635 6 163009335 PARK2 G A 12 Confidential: For Review Only 13 rs10756555 9 14459089 NFIB G A 14 rs945211 1 32191798 BAI2 G C 15 rs6478538 9 124627012 TTLL11 A G 16 rs7925100 11 118941596 VPS11 G A 17 rs75001243 7 93216002 GNGT1 C T 18 19 rs115903965 3 66009529 MAGI1 G A 20 rs4790292 17 1824305 RTN4RL1 C A 21 rs12477088 2 67841326 ETAA1 T C 22 rs1167311 1 49996959 AGBL4 G A 23 rs113079574 4 147354089 SLC10A7 C T 24 25 rs67603370 17 7524504 SHBG G A 26 rs11891707 2 207120604 ZDBF2 T C 27 rs7498044 15 92573639 SLCO3A1 G A 28 rs1933437 13 28624294 FLT3 G A 29 rs61903695 11 89922417 NAALAD2 A G 30 31 rs7305424 12 118399491 KSR2 A T 32 rs12281009 11 117032959 PAFAH1B2 A G 33 rs7913496 10 10257277 CELF2 C T 34 rs2616143 8 20632022 LZTS1 G A 35 rs7255223 19 32824310 ZNF507 C A 36 37 rs62032001 16 49065630 CBLN1 A C 38 rs2114210 8 95595162 KIAA1429 G A 39 rs149778057 13 31007805 HMGB1 A C 40 rs9529148 13 67419495 PCDH9 G A 41 rs9522180 13 111970212 TEX29 C T 42 43 rs529200 3 173114305 NLGN1 A G 44 rs2307111 5 75003678 POC5 T C 45 rs3817428 15 89415247 ACAN C G 46 rs1229984 4 100239319 ADH1B T C 47 rs11256627 10 10535954 CELF2 G A 48 49 rs6530737 8 14095763 SGCZ A G 50 rs2289379 7 44804225 ZMIZ2 C T 51 rs76187039 6 43233990 TTBK1 G T 52 rs2722406 7 24306762 NPY C T 53 rs2237402 7 39449768 POU6F2 G A 54 55 rs13275517 8 143364521 TSNARE1 T C 56 rs9265968 6 31315663 HLA-B A T 57 rs6075658 20 2094078 STK35 T C 58 rs2074686 7 100800635 AP1S1 G A 59 rs66460909 20 51195387 ZFP64 G A 60 rs75387636 10 120278394 PRLHR G A

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1 2 rs1342831 6 54096151 MLIP T C 3 rs61978655 14 30491807 PRKD1 G A 4 rs7924036 10 65191645 JMJD1C G T 5 rs2175171 1 7028842 CAMTA1 G C 6 7 rs1964926 21 42653121 BACE2 A G 8 rs1384660 2 142299735 LRP1B G A 9 rs12214497 6 10015908 OFCC1 G T 10 rs1568488 3 153657951 ARHGEF26 G C 11 rs845084 10 125220036 GPR26 G A 12 Confidential: For Review Only 13 rs12149660 16 70309237 AARS G A 14 rs12308065 12 120624085 GCN1L1 A G 15 rs187067151 20 29539588 FRG1B G T 16 rs12376870 9 117890567 TNC G A 17 rs113706999 3 44159156 TOPAZ1 T A 18 19 rs12427047 12 90213070 ATP2B1 C T 20 rs4962725 10 126733321 CTBP2 T C 21 rs115359679 7 755987 PRKAR1B C A 22 rs9652090 13 27983367 GTF3A G T 23 rs10779835 1 230299949 GALNT2 T C 24 25 rs12072739 1 98315893 DPYD A G 26 rs10498713 6 22729300 HDGFL1 G T 27 rs2744801 1 41155486 NFYC C T 28 rs3118252 9 25115154 TUSC1 G C 29 rs10503246 8 4130363 CSMD1 A G 30 31 rs6030803 20 41986507 SRSF6 T C 32 rs62134189 2 45046339 CAMKMT A G 33 rs10423928 19 46182304 GIPR T A 34 rs10234366 7 46743746 AC011294.3 G A 35 rs57654548 3 125196904 SNX4 C A 36 37 rs12630209 3 156881392 CCNL1 T G 38 rs4759228 12 56508409 PA2G4 G C 39 rs2396625 7 113028634 TSRM T A 40 rs12971645 19 45807945 MARK4 G A 41 rs78508049 1 210344884 SYT14 T C 42 43 rs556992087 12 124500725 FAM101A T C 44 rs3936511 5 55860781 AC022431.2 A G 45 rs39674 16 9413210 C16orf72 C G 46 rs273505 19 18217147 MAST3 T C 47 rs12788343 11 131452912 NTM T C 48 49 rs1451533 2 105466005 POU3F3 G A 50 rs369461388 14 40104718 FBXO33 G C 51 rs7182917 15 52080803 TMOD2 T C 52 rs13107325 4 103188709 SLC39A8 C T 53 rs62621197 19 8670147 ADAMTS10 C T 54 55 rs6050446 20 25195509 ENTPD6 A G 56 rs7808296 7 103127620 RELN C T 57 rs1324110 6 93913200 EPHA7 G C 58 rs10095724 8 53739232 RB1CC1 G A 59 rs13174863 5 139080745 CXXC5 A G 60 rs7175642 15 59450079 MYO1E T G

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1 2 rs3181269 11 33755956 CD59 C T 3 rs2229330 1 6649228 ZBTB48 T G 4 rs2187642 12 11855624 ETV6 A C 5 rs3753639 1 154986091 ZBTB7B T C 6 7 rs836179 12 50503082 GPD1 A G 8 rs6823268 4 145982563 ANAPC10 A G 9 rs34298980 6 40409243 LRFN2 T C 10 rs11655704 17 47448172 RP11-81K2.1 T C 11 rs1369159 15 66360842 MEGF11 C T 12 Confidential: For Review Only 13 rs2253310 6 108888593 FOXO3 C G 14 rs2275241 9 129370576 LMX1B G A 15 rs7331420 13 99236471 STK24 G A 16 rs67913249 5 43204126 NIM1K C G 17 rs34196306 6 27425644 ZNF184 G C 18 19 rs78517245 3 42587865 SEC22C T C 20 rs12110721 6 55190480 GFRAL G A 21 rs4500770 16 74658430 RFWD3 A T 22 rs1177279 2 61295122 KIAA1841 A G 23 rs12748436 1 177761109 SEC16B C G 24 25 rs61754230 12 72179446 RAB21 C T 26 rs9834519 3 156379637 TIPARP C T 27 rs10823826 10 53649431 PRKG1 C T 28 rs11205303 1 149906413 MTMR11 T C 29 rs2035806 10 133984916 JAKMIP3 G A 30 31 rs4545941 19 16534207 EPS15L1 T C 32 rs2343681 3 136535024 SLC35G2 G A 33 rs12713889 2 77225361 LRRTM4 T C 34 rs111584879 15 66678173 TIPIN T C 35 rs575840515 1 80796649 LPHN2 A G 36 37 rs9462670 6 41014309 OARD1 G C 38 rs2051559 4 3298800 RGS12 T C 39 rs201475383 20 26273991 FAM182B G A 40 rs12031634 1 34584393 CSMD2 G A 41 rs61985411 14 41336102 LRFN5 T A 42 43 rs61936936 12 116391685 MED13L A T 44 rs215634 7 32369148 PDE1C A G 45 rs6979832 7 127856276 LEP A G 46 rs10935143 3 134665159 EPHB1 G A 47 rs2866720 7 70106310 AUTS2 C T 48 49 rs10505836 12 19288508 PLEKHA5 A C 50 rs17029006 3 12329452 PPARG C T 51 rs2970356 15 90623540 ZNF710 C G 52 rs11150462 16 82451679 CDH13 T A 53 rs60497719 19 33971746 PEPD G A 54 55 rs13329943 16 24733751 TNRC6A C T 56 rs28839214 4 145313641 GYPA G T 57 rs12477385 2 166144850 SCN2A G T 58 rs2755253 1 67470843 SLC35D1 C T 59 rs1778830 1 156489974 IQGAP3 G A 60 rs7264802 20 62692440 TCEA2 A G

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1 2 rs7539903 1 209208033 CAMK1G T A 3 rs61986330 14 73314450 DPF3 C A 4 rs329118 5 133861663 JADE2 C T 5 rs75957461 19 11166163 SMARCA4 C T 6 7 rs6669341 1 47678458 TAL1 A G 8 rs12037905 1 219628036 SLC30A10 C T 9 rs3131336 6 28831611 TRIM27 C T 10 rs2939931 10 121636406 MCMBP T C 11 rs1865341 9 8845911 PTPRD C T 12 Confidential: For Review Only 13 rs76520838 15 47916618 SEMA6D C T 14 rs2583410 4 102182199 PPP3CA A C 15 rs7989098 13 27925496 GTF3A T C 16 rs6511826 19 12706991 ZNF490 G A 17 rs34542489 17 51917844 KIF2B A C 18 19 rs869400 3 185826740 DGKG T G 20 rs1477890 4 18511738 LCORL A G 21 rs6963840 7 78144371 MAGI2 C T 22 rs2660241 16 4940023 PPL T C 23 rs818898 9 6970806 KDM4C A G 24 25 rs12644329 4 143634746 INPP4B G A 26 rs4989244 9 102100348 SEC61B G A 27 rs35809007 2 47019521 LINC01118 G A 28 rs115866895 1 1592638 SLC35E2B A G 29 rs73085586 20 22430241 FOXA2 G A 30 31 rs7503580 17 79087036 BAIAP2 C T 32 rs4911382 20 32553095 RALY C T 33 rs7840305 8 57168101 CHCHD7 A G 34 rs16996644 20 15813475 MACROD2 C G 35 rs12992672 2 632592 TMEM18 G A 36 37 rs3815156 17 29685150 NF1 A G 38 rs4759073 12 54653258 CBX5 G A 39 rs9438393 1 205782718 SLC41A1 A G 40 rs72753485 9 96673230 BARX1 G C 41 rs1547205 9 98815145 ERCC6L2 G C 42 43 rs4648450 1 2723214 TTC34 C A 44 rs724623 14 47303577 MDGA2 A C 45 rs35162296 6 26318262 HIST1H4H C T 46 rs1899689 7 121964349 CADPS2 C T 47 rs78886584 1 16859325 FAM231B A G 48 49 rs9594686 13 42723197 DGKH C T 50 rs1598121 3 82694710 GBE1 A G 51 rs9888533 13 107854612 FAM155A C T 52 rs2576135 13 54691442 OLFM4 T A 53 rs7511698 1 25015638 SRRM1 C T 54 55 rs28711392 11 13349559 ARNTL T C 56 rs7549358 1 115252609 NRAS G C 57 rs1905616 8 93235675 RUNX1T1 G A 58 rs6752979 2 81741750 CTNNA2 G A 59 rs6449532 5 60715446 ZSWIM6 C T 60 rs7020196 9 12289527 TYRP1 C T

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1 2 rs368540015 7 74292165 GTF2IRD2 A G 3 rs6761463 2 50201547 NRXN1 G C 4 rs35390852 4 143067054 INPP4B G A 5 rs6583310 3 196170985 UBXN7 G C 6 7 rs1987960 20 30649834 HCK T C 8 rs115778101 1 78198554 USP33 T C 9 rs10116891 9 122651993 RP11-295D22.1 G A 10 rs12450028 17 2207425 SRR C T 11 rs537508 4 171042158 AADAT G C 12 Confidential: For Review Only 13 rs7020564 9 109670016 ZNF462 A T 14 rs10953577 7 108263540 DNAJB9 T C 15 rs34994596 15 80991447 ABHD17C T C 16 rs34373881 3 20432033 SGOL1 G A 17 rs45521740 19 2245622 SF3A2 G A 18 19 rs200801362 6 31555480 LST1 T C 20 rs2629881 3 59778271 FHIT C T 21 rs4663213 2 236807893 AGAP1 G A 22 rs112852122 20 47498117 ARFGEF2 G A 23 rs9615723 22 48386670 FAM19A5 C T 24 25 rs9370527 6 56245812 COL21A1 G A 26 rs11513729 12 112273499 MAPKAPK5 C T 27 rs1476698 2 242296449 FARP2 A G 28 rs7239114 18 45921214 ZBTB7C G A 29 rs533493779 2 104447054 TMEM182 A T 30 31 rs11765062 7 54417515 VSTM2A T C 32 rs1409158 1 119538890 TBX15 C T 33 rs1333010 13 66205228 PCDH9 G A 34 rs12885251 14 99670791 BCL11B G A 35 rs77976727 8 4300554 CSMD1 C T 36 37 rs8015400 14 25930988 STXBP6 C A 38 rs10842356 12 24621348 BCAT1 A T 39 rs142503704 5 92622421 NR2F1 G A 40 rs4723263 7 33194826 BBS9 G C 41 rs73422097 6 41727740 PGC A G 42 43 rs13061117 3 181186466 SOX2 T C 44 rs61937656 12 39483502 CPNE8 G A 45 rs4575195 10 114765747 TCF7L2 C A 46 rs1040046 6 83473573 UBE3D C A 47 rs788163 2 172931559 METAP1D A C 48 49 rs686431 6 35974217 SLC26A8 C T 50 rs2246623 17 74084449 EXOC7 C T 51 rs78907487 22 22151939 MAPK1 A C 52 rs7103389 11 881639 CHID1 T C 53 rs12927792 16 9713194 RP11-297M9.1 C T 54 55 rs2083323 18 1856272 METTL4 G A 56 rs13218383 6 120173501 MAN1A1 C G 57 rs9673839 16 76895693 RP11-58C22.1 A G 58 rs2186118 1 66456465 PDE4B C A 59 rs4074404 1 187683956 PLA2G4A T A 60 rs35193668 13 33092929 N4BP2L2 C T

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1 2 rs698147 5 3513485 IRX1 A G 3 rs3806114 6 20482335 E2F3 G A 4 rs1704190 2 200760629 C2orf69 G A 5 rs10860295 12 98542699 RP11-181C3.1 T C 6 7 rs139497 22 41640098 RANGAP1 C T 8 rs868784 11 43944388 C11orf96 G A 9 rs6597653 9 133788465 FIBCD1 G C 10 rs11215403 11 115058585 CADM1 G A 11 rs146980124 17 44627649 ARL17A A C 12 Confidential: For Review Only 13 rs1799507 12 16427314 SLC15A5 G A 14 rs7141912 14 35649431 KIAA0391 A T 15 rs212517 1 21577159 ECE1 T A 16 rs12213441 6 143208838 HIVEP2 C T 17 rs9603697 13 40783323 AL133318.1 C T 18 19 rs36131051 3 107888841 IFT57 T G 20 rs10896348 11 68357368 PPP6R3 T C 21 rs9852062 3 45373442 LARS2 T A 22 rs7162542 15 84514290 ADAMTSL3 C G 23 rs1286138 14 91485445 RPS6KA5 T G 24 25 rs7759938 6 105378954 LIN28B C T 26 rs78565420 8 85703065 RALYL C T 27 rs79675564 2 211286896 LANCL1 C A 28 rs16940823 18 22137319 HRH4 C A 29 rs12951079 17 34933059 GGNBP2 G A 30 31 rs7038966 9 73777777 TRPM3 C T 32 rs10760277 9 126093999 CRB2 C T 33 rs11040333 11 49346332 FOLH1 G A 34 rs10823504 10 72034062 NPFFR1 G A 35 rs7518221 1 225561346 DNAH14 T C 36 37 rs7931626 11 28421841 METTL15 C T 38 rs66674732 13 62721160 PCDH20 G A 39 rs9579775 13 20616557 ZMYM2 A C 40 rs544957562 9 33978015 UBAP2 A T 41 rs4432271 16 20245283 GP2 C T 42 43 rs80082351 3 114415926 ZBTB20 A G 44 rs16839832 1 196349909 KCNT2 G T 45 rs76824303 3 62459819 CADPS A C 46 rs544200874 4 20124826 SLIT2 C T 47 rs113132247 9 131026108 GOLGA2 G A 48 49 rs62379271 5 105870033 EFNA5 T G 50 rs11047138 12 24019853 SOX5 C G 51 rs7086898 10 104386152 SUFU A G 52 rs57488047 15 79403002 RASGRF1 T C 53 rs11856579 15 78012688 LINGO1 G A 54 55 rs12147845 14 101144596 DLK1 C T 56 rs7606059 2 188152749 CALCRL T C 57 rs8124896 20 21385659 NKX2-4 T C 58 rs4677813 3 194863860 XXYLT1 T C 59 rs884152 8 25770557 EBF2 G T 60 rs34811474 4 25408838 ANAPC4 G A

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1 2 rs76702514 1 195148296 KCNT2 C G 3 rs12821683 12 58588964 XRCC6BP1 G C 4 rs73078357 3 48695834 CELSR3 T C 5 rs7869098 9 27816218 LINGO2 T G 6 7 rs12462975 19 30272202 CCNE1 G A 8 rs114728753 3 78483402 ROBO1 A C 9 rs7565437 2 65646966 SPRED2 T C 10 rs9788550 14 29681138 PRKD1 G C 11 rs680071 11 103088414 DYNC2H1 T C 12 Confidential: For Review Only 13 rs1222216 11 30346052 ARL14EP C T 14 rs12634936 3 147716498 ZIC1 T C 15 rs4677156 3 72417857 RYBP A T 16 rs329651 11 133767622 IGSF9B G T 17 rs4783789 16 51446707 SALL1 T C 18 19 rs12363672 11 55684028 OR5W2 A C 20 rs10457469 6 126083658 HEY2 G A 21 rs2034963 3 48170802 CDC25A G C 22 rs7719067 5 153538241 MFAP3 A G 23 rs117455294 20 57427951 GNAS C A 24 25 rs2207894 20 54387343 CBLN4 C T 26 rs146910503 2 25446473 DNMT3A G A 27 rs1805123 7 150645534 KCNH2 T G 28 rs10791113 11 130873165 SNX19 A G 29 rs796915 6 154304628 OPRM1 C G 30 31 rs72755233 15 100692953 ADAMTS17 G A 32 rs10146997 14 79945162 NRXN3 A G 33 rs3823674 7 50571996 DDC C T 34 rs72652703 8 67209548 CRH T C 35 rs35221880 12 133301500 ANKLE2 T C 36 37 rs1775255 6 51243035 PKHD1 G T 38 rs7145882 14 103255461 TRAF3 T C 39 rs7814267 8 5545084 CSMD1 A G 40 rs6679458 1 96946253 PTBP2 G T 41 rs114593013 3 84113491 CADM2 A G 42 43 rs12454712 18 60845884 BCL2 T C 44 rs2157295 22 42701984 TCF20 T G 45 rs1436348 3 104612668 ALCAM A G 46 rs201666051 9 20920868 FOCAD C T 47 rs10736156 10 104019447 GBF1 C A 48 49 rs6606686 12 110903380 GPN3 G C 50 rs1582931 5 122657199 CEP120 G A 51 rs11633022 15 73074890 ADPGK C A 52 rs74080008 1 51047717 FAF1 G T 53 rs11209943 1 72750500 NEGR1 A G 54 55 rs2875762 6 124925032 NKAIN2 G C 56 rs2238435 16 4014282 ADCY9 C G 57 rs34292685 11 64049021 GPR137 C T 58 rs12941038 17 66509143 PRKAR1A C T 59 rs6719507 2 29733801 ALK G A 60 rs347551 5 119389031 PRR16 C G

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1 2 rs2425856 20 44911954 CDH22 A G 3 rs651533 1 82375561 LPHN2 T A 4 rs4764949 12 103658096 C12orf42 A G 5 rs28465175 15 53427155 ONECUT1 A G 6 7 rs4482463 2 205375909 PARD3B C A 8 rs7230240 18 42597978 SETBP1 C T 9 rs9291816 5 63932508 RGS7BP C T 10 rs7749708 6 153375907 RGS17 C T 11 rs10799778 1 23313353 LACTBL1 T G 12 Confidential: For Review Only 13 rs3129942 6 32338283 C6orf10 G T 14 rs4467770 6 12086826 HIVEP1 G A 15 rs11000993 10 76084111 ADK T C 16 rs114263339 5 50932343 ISL1 C T 17 rs7354849 1 232765308 SIPA1L2 A G 18 19 rs1320903 3 131758077 CPNE4 G A 20 rs3791478 2 240064139 HDAC4 T C 21 rs1619120 9 87302196 NTRK2 A G 22 rs6843852 4 162132758 FSTL5 C T 23 rs7672 16 68294800 PLA2G15 C G 24 25 rs8030456 15 68076856 MAP2K5 C T 26 rs113962925 17 46044446 CDK5RAP3 C T 27 rs1381010 4 112677085 C4orf32 G A 28 rs762705 3 50313527 LSMEM2 A C 29 rs1296685 22 18230964 BID A G 30 31 rs947088 20 17171373 PCSK2 G T 32 rs3172332 3 153973408 ARHGEF26 T C 33 rs3125326 10 63053788 TMEM26 A C 34 rs3902951 14 69789755 GALNT16 T G 35 rs28462076 4 65696174 TECRL A G 36 37 rs9260164 6 29911684 HLA-A C T 38 rs55726687 12 991306 WNK1 G A 39 rs1373349 18 63282992 CDH7 C T 40 rs7123283 11 122809055 C11orf63 C T 41 rs1452991 6 141473363 NMBR G A 42 43 rs74929176 17 54905494 C17orf67 C T 44 rs72917533 2 175238924 CIR1 T C 45 rs12705894 7 113351252 PPP1R3A G A 46 rs77560793 1 175001179 MRPS14 G A 47 rs7355953 3 85792137 CADM2 T C 48 49 rs8096658 18 77156537 NFATC1 C G 50 rs11642090 16 81730582 CMIP T C 51 rs661878 11 29188691 METTL15 A G 52 rs9480184 6 155987788 NOX3 C T 53 rs815163 1 190294726 BRINP3 T C 54 55 rs4958568 5 152016093 NMUR2 G A 56 rs11218510 11 121922587 BLID G A 57 rs1788808 18 21090023 NPC1 A G 58 rs2542615 10 131128952 MGMT C T 59 rs4672338 2 60217457 BCL11A C T 60 rs4792716 17 15943144 NCOR1 A G

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1 2 rs1296328 4 137083193 PCDH18 A C 3 rs6029180 20 39178923 MAFB A G 4 rs12883788 14 33303540 AKAP6 C T 5 rs10133279 14 82702712 SEL1L C T 6 7 rs61909165 11 134589355 AP003062.1 T A 8 rs61746970 19 51132746 SYT3 G A 9 rs1696057 12 90767160 CCER1 T C 10 rs143662847 8 48804722 PRKDC C T 11 rs1199333 3 138091701 MRAS G T 12 Confidential: For Review Only 13 rs12641981 4 45179883 GNPDA2 C T 14 rs39862 5 66185151 MAST4 T C 15 rs2735556 3 88105360 CGGBP1 T C 16 rs1013737 18 937050 ADCYAP1 G C 17 rs2141004 2 6194359 DKFZP761K2322 A C 18 19 rs6069625 20 54747469 MC3R A G 20 rs2658797 11 93212254 SMCO4 C T 21 rs67257872 11 8530218 STK33 A G 22 rs12187066 5 88800355 MEF2C A G 23 rs62425398 6 166416028 PDE10A C A 24 25 rs2268762 3 38516075 ACVR2B A G 26 rs8038574 15 95275890 MCTP2 T C 27 rs62277889 2 198783693 PLCL1 C T 28 rs7498665 16 28883241 SH2B1 A G 29 rs11223204 11 132652554 OPCML A G 30 31 rs9814758 3 123062657 ADCY5 T G 32 rs56803094 15 99222509 IGF1R A G 33 rs2247401 15 53156672 ONECUT1 G A 34 rs79686965 11 46020909 PHF21A A G 35 rs6798941 3 52893465 TMEM110 C T 36 37 rs11525873 7 138817193 TTC26 T C 38 rs7102934 11 84648068 DLG2 T C 39 rs4971239 1 203491150 OPTC G A 40 rs148137538 1 173399677 PRDX6 A G 41 rs8130408 21 39237138 KCNJ6 A C 42 43 rs200744777 20 6609610 BMP2 T G 44 rs7550711 1 110082886 GPR61 C T 45 rs57590313 4 113323430 ALPK1 C A 46 rs10796828 11 69490346 ORAOV1 T G 47 rs78607331 12 57648644 R3HDM2 C T 48 49 rs17399739 10 87490850 GRID1 A G 50 rs1402989 3 27056851 NEK10 C T 51 rs17773370 18 57951433 MC4R G A 52 rs41310284 10 102447647 PAX2 C A 53 rs112859723 3 131625376 CPNE4 T C 54 55 rs3748126 7 76632736 UPK3B C G 56 rs9610387 22 36476762 RBFOX2 G A 57 rs2281148 20 36433288 CTNNBL1 T C 58 rs35894137 8 43071838 HGSNAT C T 59 rs594585 16 65939803 CDH5 T G 60 rs2968973 4 130740404 C4orf33 C T

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1 2 rs6548220 2 225951 SH3YL1 A G 3 rs113230003 19 18460956 PGPEP1 G A 4 rs811054 16 72251132 PMFBP1 C T 5 rs7439324 4 44501351 KCTD8 C T 6 7 rs59893724 5 80830788 SSBP2 A G 8 rs13047416 21 40309436 ETS2 C G 9 rs8111074 19 51776117 SIGLECL1 G T 10 rs10969334 9 29717279 LINGO2 C A 11 rs6601451 8 10243681 MSRA C G 12 Confidential: For Review Only 13 rs10790809 11 126372550 KIRREL3 A G 14 rs4688359 3 61198880 FHIT C T 15 rs62171698 2 143959096 ARHGAP15 C A 16 rs538579 3 62711674 CADPS G C 17 rs11134679 5 170623391 RANBP17 A G 18 19 rs17619860 8 87779603 CNGB3 T C 20 rs630602 1 54728864 SSBP3 G C 21 rs12517187 5 112444682 MCC C T 22 rs138329430 1 174619318 RABGAP1L G A 23 rs1517037 18 56878274 GRP C T 24 25 rs34778589 22 50709957 MAPK11 A C 26 rs56094641 16 53806453 FTO A G 27 rs10887571 10 88030441 GRID1 C T 28 rs2450444 10 93010383 PCGF5 G A 29 rs2417998 9 111958746 EPB41L4B C G 30 31 rs10111937 8 54160092 OPRK1 C T 32 rs8117463 20 17231063 PCSK2 G A 33 rs7536458 1 118864602 SPAG17 T G 34 rs10749659 1 151033979 MLLT11 C T 35 rs68015088 18 51484010 MBD2 G A 36 37 rs12429545 13 54102206 OLFM4 G A 38 rs6870983 5 87697533 TMEM161B C T 39 rs112875651 8 126506694 TRIB1 G A 40 rs719802 11 113234679 TTC12 T C 41 rs827803 3 157920266 RSRC1 G T 42 43 rs2234458 11 65639374 EFEMP2 C T 44 rs79236537 5 86727690 CCNH G T 45 rs8008772 14 88321884 GALC A T 46 rs957512 9 120405705 TLR4 T C 47 rs142315514 1 147050816 BCL9 C A 48 49 rs7012648 8 28091482 ELP3 G A 50 rs7753558 6 117523471 VGLL2 C A 51 rs4739558 8 38337264 FGFR1 A G 52 rs73982435 17 31473455 ASIC2 C T 53 rs512121 18 7548501 PTPRM T C 54 55 rs7453694 6 51739528 PKHD1 C T 56 rs12045879 1 15817090 CELA2B C T 57 rs59714050 3 141267294 RASA2 T A 58 rs1633418 22 20091756 DGCR8 T C 59 rs3861871 9 129424719 LMX1B A G 60 rs11496125 7 103417557 RELN C T

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1 2 rs7951870 11 46373311 DGKZ T C 3 rs12798028 11 47604639 NDUFS3 C T 4 rs559231 18 39644247 PIK3C3 G T 5 rs73026723 19 31017177 ZNF536 C T 6 7 rs4148155 4 89054667 ABCG2 A G 8 rs7656673 4 30840331 PCDH7 A G 9 rs3810291 19 47569003 ZC3H4 G A 10 rs72892910 6 50816887 TFAP2B G T 11 rs7711823 5 158489315 EBF1 A G 12 Confidential: For Review Only 13 rs34722008 4 38659594 AC021860.1 G A 14 rs75706763 2 145669168 ZEB2 A G 15 rs12484438 22 40558064 TNRC6B T C 16 rs55658481 2 219284215 VIL1 G A 17 rs11976084 7 137437156 DGKI C T 18 19 rs58084604 18 57849429 MC4R C T 20 rs1852006 7 77829768 MAGI2 G A 21 rs2712667 12 99588917 ANKS1B G C 22 rs55896564 8 11447093 BLK G A 23 rs55838622 5 95711605 PCSK1 A C 24 25 rs1422067 5 77424836 AP3B1 C T 26 rs9922288 16 24550930 RBBP6 A G 27 rs10791902 11 67093360 SSH3 C T 28 rs11150745 17 78757626 RPTOR A G 29 rs72618637 2 48953979 GTF2A1L T A 30 31 rs7752998 6 34398358 RPS10 A T 32 rs111768603 3 42329113 CCK G T 33 rs7619139 3 25110415 RARB T A 34 rs3931548 9 103113652 TEX10 C A 35 rs80082536 3 35195311 ARPP21 A G 36 37 rs7827182 8 8380471 SGK223 G C 38 rs4836133 5 124332103 ZNF608 C A 39 rs62004865 15 74207695 LOXL1 T A 40 rs7928320 11 116942753 SIK3 C G 41 rs59428052 2 53861389 GPR75-ASB3 A G 42 43 rs8089514 18 69224478 RP11-723G8.2 T A 44 rs1576655 13 79587841 RBM26 A C 45 rs12606230 18 52492252 RAB27B T C 46 rs72673947 8 118884379 EXT1 A G 47 rs61992671 14 101531854 AL117190.3 A G 48 49 rs62048187 15 38117049 TMCO5A G C 50 rs57636386 18 58048295 MC4R T C 51 rs1423534 5 63977000 FAM159B G A 52 rs35775580 7 130420740 KLF14 A G 53 rs112253053 19 19425145 SUGP1 T A 54 55 rs28350 3 42418446 LYZL4 A G 56 rs1834144 18 40744790 RIT2 C A 57 rs12140153 1 62579891 INADL G T 58 rs9317002 13 59175727 PCDH17 C A 59 60

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1 Supplementary Table 4: Comparison of genome-wide effect estimates between2 early life and adult body size in the UK Biobank SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Beta (Adult) SE (Adult) P (Adult) Beta (Age 10) SE (Age 10) P (Age 10) 7 -0.0118066 0.00140063 3.50E-17 0.00589934 0.00143123 3.80E-05 8 0.0104426 0.00138041 3.90E-14 0.0274603 0.0014112 2.50E-84 9 0.00564903 0.00144394 9.10E-05 -0.0125693 0.00147501 1.60E-17 10 -0.0166763 0.00498629 0.00082 0.042032 0.00509751 1.60E-16 11 12 -0.0175503Confidential:0.00137056 1.50E-37 For-0.00406936 Review0.00140159 Only0.0037 13 -0.00624158 0.00146057 1.90E-05 0.0105292 0.00149263 1.70E-12 14 0.000944429 0.00144792 0.51 -0.0157627 0.00147894 1.60E-26 15 -0.00853653 0.00139856 1.00E-09 0.00394057 0.00142889 0.0058 16 0.0100376 0.0014969 2.00E-11 -0.00346122 0.00152911 0.024 17 18 0.0123928 0.00138267 3.20E-19 -0.00036868 0.00141185 0.79 19 -0.0186209 0.00141036 8.40E-40 -0.0312648 0.00144009 1.60E-104 20 -0.0301239 0.00169429 1.00E-70 -0.0471181 0.00173208 6.00E-163 21 0.0126785 0.00139004 7.40E-20 0.00133392 0.00141995 0.35 22 23 0.000576386 0.00151019 0.7 0.0122893 0.00154345 1.70E-15 24 -0.0199485 0.00136878 4.10E-48 -0.0359119 0.00139965 3.50E-145 25 -0.0113095 0.00296902 0.00014 -0.0423448 0.00303598 3.30E-44 26 -0.0118089 0.00154676 2.30E-14 0.00101877 0.00157954 0.52 27 -0.0155163 0.00146443 3.10E-26 -0.00384235 0.00149581 0.01 28 29 0.0125361 0.00138627 1.50E-19 -0.00147231 0.00141598 0.3 30 -0.0144693 0.00143954 9.10E-24 -0.0012696 0.00147066 0.39 31 0.0160691 0.00190178 2.90E-17 -0.00345424 0.00194151 0.075 32 0.0228315 0.00248522 4.00E-20 -0.00115027 0.00253762 0.65 33 -0.0127637 0.00176726 5.10E-13 0.00177773 0.00180586 0.32 34 35 -0.00326079 0.0014499 0.025 0.00886901 0.00148224 2.20E-09 36 0.0126512 0.00190443 3.10E-11 -0.0020999 0.00194422 0.28 37 -0.00136324 0.0017049 0.42 -0.0153659 0.00174293 1.20E-18 38 -0.00406274 0.00173954 0.02 0.0100289 0.00177714 1.70E-08 39 -0.00236251 0.00164269 0.15 -0.0178193 0.00167858 2.50E-26 40 41 -0.0132548 0.00201085 4.30E-11 0.00225962 0.00205477 0.27 42 -0.00978895 0.00146872 2.60E-11 4.55E-05 0.00150014 0.98 43 -0.0152449 0.00149355 1.80E-24 -0.000569076 0.00152569 0.71 44 0.0245417 0.00175291 1.50E-44 0.0117028 0.00179063 6.30E-11 45 -0.0136135 0.00146958 2.00E-20 -9.61E-06 0.00150144 0.99 46 47 0.00868308 0.00144114 1.70E-09 -0.00064613 0.00147277 0.66 48 0.0162355 0.00171408 2.70E-21 0.00470841 0.00175096 0.0072 49 0.0167586 0.00215398 7.20E-15 -0.00143349 0.00220054 0.51 50 0.0142008 0.0014016 4.00E-24 0.00397895 0.00143321 0.0055 51 0.0150324 0.00182987 2.10E-16 0.00198417 0.00187003 0.29 52 53 -0.0151686 0.00241102 3.10E-10 -0.000292565 0.00246561 0.91 54 -0.0177511 0.00293025 1.40E-09 0.00133971 0.00299659 0.65 55 -0.0104412 0.00156447 2.50E-11 0.00149155 0.00159839 0.35 56 0.000909527 0.00168998 0.59 -0.00950759 0.00172531 3.60E-08 57 0.0226623 0.00376431 1.70E-09 0.000121726 0.00384367 0.97 58 59 -0.00220462 0.00140295 0.12 0.00807228 0.00143424 1.80E-08 60 -0.00230822 0.0013764 0.094 0.00893011 0.00140744 2.20E-10 0.00980287 0.0014192 4.90E-12 -0.000757207 0.00145086 0.6

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1 2 -0.00995498 0.00141493 2.00E-12 0.00143567 0.00144551 0.32 3 0.00210708 0.0017896 0.24 0.015449 0.00183012 3.10E-17 4 0.00969144 0.00167974 7.90E-09 0.000465637 0.00171515 0.79 5 -0.0101768 0.00145748 2.90E-12 -0.00193319 0.00148908 0.19 6 7 0.00863143 0.00143586 1.80E-09 -0.00100543 0.00146675 0.49 8 0.00824166 0.00146708 1.90E-08 0.00111736 0.00149928 0.46 9 -0.00945149 0.00169839 2.60E-08 0.00114819 0.0017351 0.51 10 -0.0124381 0.00176815 2.00E-12 0.00149441 0.00180604 0.41 11 0.00809436 0.00143164 1.60E-08 -0.00233632 0.00146232 0.11 12 Confidential: For Review Only 13 -0.00780228 0.00137254 1.30E-08 0.00206294 0.00140349 0.14 14 0.0122831 0.00136952 3.00E-19 0.00123916 0.00140053 0.38 15 0.00896084 0.00156363 1.00E-08 -0.00062795 0.00159851 0.69 16 0.0112311 0.00142704 3.50E-15 -0.000364773 0.00145922 0.8 17 -0.0101252 0.00152324 3.00E-11 0.000162024 0.00155575 0.92 18 19 -0.0150162 0.00144491 2.70E-25 -0.00575098 0.00147714 9.90E-05 20 -0.00848296 0.00141586 2.10E-09 0.00185106 0.00144744 0.2 21 0.0101003 0.00142485 1.40E-12 -0.000730481 0.00145623 0.62 22 0.00951719 0.00137849 5.10E-12 -0.00091675 0.0014097 0.52 23 0.00944934 0.00155587 1.30E-09 -0.000583709 0.00159095 0.71 24 25 -0.014757 0.00137637 8.10E-27 -0.00608707 0.00140582 1.50E-05 26 0.010504 0.00146427 7.30E-13 0.000690913 0.00149729 0.64 27 0.0128653 0.00229443 2.10E-08 -0.00220489 0.00234351 0.35 28 0.0136423 0.00183985 1.20E-13 9.35E-05 0.00188089 0.96 29 -0.0106156 0.00189063 2.00E-08 0.00206605 0.00193343 0.29 30 31 -0.0121794 0.00138306 1.30E-18 -0.00186034 0.00141136 0.19 32 0.0138512 0.00176589 4.40E-15 0.0006307 0.00180278 0.73 33 -0.00367597 0.00326088 0.26 -0.0245792 0.00333076 1.60E-13 34 -0.0125644 0.00177792 1.60E-12 -0.00191964 0.00181544 0.29 35 -0.00809618 0.00139493 6.50E-09 0.00115585 0.00142565 0.42 36 37 0.0259588 0.00396473 5.90E-11 0.00409363 0.00405317 0.31 38 0.0114218 0.00138666 1.80E-16 0.00154584 0.00141793 0.28 39 0.0146376 0.00197063 1.10E-13 0.00124259 0.00201403 0.54 40 0.0119925 0.00195352 8.30E-10 0.000884198 0.0019971 0.66 41 0.00810079 0.00145332 2.50E-08 -0.0009635 0.00148574 0.52 42 43 0.0100464 0.00155554 1.10E-10 -0.000664623 0.00158952 0.68 44 0.0102433 0.00139113 1.80E-13 -0.000288029 0.00142177 0.84 45 0.00754945 0.00137666 4.20E-08 -0.00126483 0.00140698 0.37 46 -0.0117042 0.00150889 8.70E-15 -0.000768842 0.00154305 0.62 47 0.0168634 0.00196315 8.70E-18 0.0298545 0.00200515 3.90E-50 48 49 -0.00971808 0.00143319 1.20E-11 0.000824495 0.00146403 0.57 50 0.00975752 0.00149027 5.90E-11 0.000665362 0.00152282 0.66 51 0.000916599 0.00137129 0.5 0.00938062 0.00139994 2.10E-11 52 -0.0121927 0.00138837 1.60E-18 -0.00152667 0.00141848 0.28 53 -0.0097792 0.00386646 0.011 -0.0322531 0.00394917 3.20E-16 54 55 0.0591385 0.00318191 4.20E-77 0.0802051 0.00325367 3.60E-134 56 -0.00779677 0.00142034 4.00E-08 0.000768208 0.00144941 0.6 57 -0.0246975 0.00211727 1.90E-31 -0.0137682 0.0021645 2.00E-10 58 -0.0218858 0.00374062 4.90E-09 0.000639291 0.00382301 0.87 59 -0.00805227 0.00141346 1.20E-08 0.00174034 0.00144375 0.23 60 -0.0151299 0.00233311 8.90E-11 0.000377044 0.00238515 0.87

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1 2 3 4 5 6 Interaction P 7 9.86E-15 8 7.27E-14 9 1.71E-13 10 1.03E-11 11 12 1.29E-11Confidential: For Review Only 13 1.93E-11 14 2.38E-11 15 5.97E-10 16 7.16E-10 17 18 9.27E-10 19 3.98E-09 20 4.69E-09 21 1.03E-08 22 23 1.54E-08 24 1.94E-08 25 2.31E-08 26 2.39E-08 27 3.51E-08 28 29 4.17E-08 30 4.65E-08 31 1.05E-07 32 1.27E-07 33 1.55E-07 34 35 1.75E-07 36 2.96E-07 37 4.19E-07 38 4.19E-07 39 4.38E-07 40 41 7.00E-07 42 7.11E-07 43 8.10E-07 44 8.17E-07 45 8.77E-07 46 47 9.73E-07 48 1.05E-06 49 1.27E-06 50 1.39E-06 51 1.41E-06 52 53 1.91E-06 54 2.35E-06 55 2.67E-06 56 3.03E-06 57 3.35E-06 58 59 3.35E-06 60 4.02E-06 4.14E-06

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1 2 5.37E-06 3 5.52E-06 4 5.56E-06 5 6.09E-06 6 7 6.93E-06 8 7.23E-06 9 8.06E-06 10 9.24E-06 11 9.52E-06 12 Confidential: For Review Only 13 9.85E-06 14 9.97E-06 15 1.00E-05 16 1.01E-05 17 1.22E-05 18 19 1.25E-05 20 1.27E-05 21 1.27E-05 22 1.31E-05 23 1.37E-05 24 25 1.38E-05 26 1.39E-05 27 1.65E-05 28 1.68E-05 29 1.74E-05 30 31 1.82E-05 32 2.12E-05 33 2.27E-05 34 2.34E-05 35 2.61E-05 36 37 2.62E-05 38 2.83E-05 39 3.02E-05 40 3.09E-05 41 3.15E-05 42 43 3.54E-05 44 3.59E-05 45 3.66E-05 46 3.85E-05 47 3.86E-05 48 49 4.14E-05 50 4.20E-05 51 4.42E-05 52 4.80E-05 53 5.56E-05 54 55 6.25E-05 56 6.61E-05 57 6.85E-05 58 6.93E-05 59 7.01E-05 60 7.07E-05

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1 2 7.16E-05 3 7.16E-05 4 7.27E-05 5 7.47E-05 6 7 8.06E-05 8 8.09E-05 9 8.21E-05 10 8.62E-05 11 8.94E-05 12 Confidential: For Review Only 13 9.22E-05 14 9.26E-05 15 9.43E-05 16 9.59E-05 17 9.81E-05 18 19 0.000109213 20 0.000120473 21 0.000132466 22 0.000141612 23 0.000144836 24 25 0.000152674 26 0.00015344 27 0.000163603 28 0.000175851 29 0.000181139 30 31 0.000192773 32 0.000201214 33 0.000201884 34 0.000206214 35 0.000209617 36 37 0.000212647 38 0.000215316 39 0.000222604 40 0.00022643 41 0.000233642 42 43 0.000244918 44 0.000244933 45 0.000246864 46 0.000249312 47 0.000256988 48 49 0.000268478 50 0.000268808 51 0.000293454 52 0.000294332 53 0.000342333 54 55 0.000364415 56 0.000365358 57 0.00037583 58 0.00038693 59 0.000388444 60 0.000390225

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1 2 0.000393968 3 0.000402594 4 0.000431868 5 0.000475997 6 7 0.000490051 8 0.000491534 9 0.000495967 10 0.000499345 11 0.000503232 12 Confidential: For Review Only 13 0.000521384 14 0.000549797 15 0.000549858 16 0.000562663 17 0.000577066 18 19 0.000583042 20 0.000585354 21 0.000592664 22 0.00060031 23 0.000625365 24 25 0.000630657 26 0.000634271 27 0.000643918 28 0.000669335 29 0.000673366 30 31 0.000702164 32 0.000721358 33 0.000729881 34 0.000776743 35 0.000824916 36 37 0.000829762 38 0.00086213 39 0.000872792 40 0.000877137 41 0.000900439 42 43 0.000944909 44 0.000985926 45 0.000992744 46 0.00100118 47 0.001021964 48 49 0.0010285 50 0.001037734 51 0.00110337 52 0.001111925 53 0.001115259 54 55 0.001153103 56 0.001174181 57 0.001204816 58 0.001206579 59 0.001210798 60 0.00123912

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1 2 0.001307653 3 0.00133326 4 0.001397206 5 0.00146817 6 7 0.001474258 8 0.00147509 9 0.001539182 10 0.001551411 11 0.001627574 12 Confidential: For Review Only 13 0.001631333 14 0.00164832 15 0.001659169 16 0.001717058 17 0.001720265 18 19 0.001734809 20 0.001742347 21 0.001746701 22 0.001769475 23 0.001774496 24 25 0.0017943 26 0.001858577 27 0.001895866 28 0.001900696 29 0.00199555 30 31 0.002028836 32 0.002050018 33 0.00211467 34 0.002125456 35 0.002125859 36 37 0.002160357 38 0.002198607 39 0.002227643 40 0.00230992 41 0.002310363 42 43 0.00231643 44 0.002361185 45 0.002367457 46 0.002375076 47 0.00271708 48 49 0.002749541 50 0.002858211 51 0.002950311 52 0.002989822 53 0.003050638 54 55 0.003073386 56 0.003151586 57 0.003227397 58 0.003251315 59 0.003469566 60 0.003498348

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1 2 0.003637126 3 0.00375035 4 0.003789832 5 0.003910227 6 7 0.003938384 8 0.003992638 9 0.004016212 10 0.00410523 11 0.004113603 12 Confidential: For Review Only 13 0.004187978 14 0.004289318 15 0.004294773 16 0.004371666 17 0.004398136 18 19 0.004419839 20 0.00444215 21 0.004549716 22 0.004786429 23 0.004886058 24 25 0.005124163 26 0.005191597 27 0.005241267 28 0.005443306 29 0.005464625 30 31 0.0055171 32 0.00551951 33 0.005543345 34 0.005645054 35 0.005761362 36 37 0.005871044 38 0.005888223 39 0.005939936 40 0.006038232 41 0.006041274 42 43 0.006078032 44 0.006335508 45 0.006358941 46 0.006363082 47 0.006443831 48 49 0.006551459 50 0.006609749 51 0.006643579 52 0.006853195 53 0.007059581 54 55 0.007147804 56 0.007474707 57 0.007519801 58 0.007829571 59 0.007969598 60 0.007978942

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1 2 0.008176092 3 0.008204722 4 0.008215378 5 0.008255818 6 7 0.008406413 8 0.008422635 9 0.008443093 10 0.008481064 11 0.008516992 12 Confidential: For Review Only 13 0.008536224 14 0.008591386 15 0.008852163 16 0.008887634 17 0.008989157 18 19 0.009048169 20 0.009381794 21 0.009431928 22 0.009447561 23 0.009558092 24 25 0.009713174 26 0.009727535 27 0.010094931 28 0.010293043 29 0.010334787 30 31 0.010385599 32 0.010644474 33 0.010975357 34 0.011014364 35 0.0111035 36 37 0.011565044 38 0.011653261 39 0.01170179 40 0.011931028 41 0.012072566 42 43 0.012291742 44 0.012362303 45 0.01237244 46 0.012386562 47 0.012391498 48 49 0.012783336 50 0.012895303 51 0.013187276 52 0.013214562 53 0.013338296 54 55 0.013467765 56 0.013572218 57 0.01402263 58 0.014032948 59 0.014363953 60 0.014377489

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1 2 0.276509421 3 0.280971432 4 0.286395592 5 0.287707649 6 7 0.288704892 8 0.291614011 9 0.304078732 10 0.304553404 11 0.304600637 12 Confidential: For Review Only 13 0.305722951 14 0.312934541 15 0.314524625 16 0.322558606 17 0.323487587 18 19 0.329240238 20 0.337007832 21 0.339654761 22 0.342074358 23 0.346715769 24 25 0.347023385 26 0.356936285 27 0.362884726 28 0.36473487 29 0.365991085 30 31 0.366501416 32 0.378106465 33 0.381042455 34 0.387013605 35 0.390853466 36 37 0.393230202 38 0.394624196 39 0.396061157 40 0.399898646 41 0.402080035 42 43 0.405530475 44 0.407248678 45 0.415017328 46 0.417440374 47 0.42898166 48 49 0.430287508 50 0.432940184 51 0.446523149 52 0.465811913 53 0.476966036 54 55 0.477819349 56 0.47958885 57 0.487035858 58 0.491327207 59 0.493601675 60 0.500013878

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1 2 0.52090774 3 0.527357034 4 0.531546264 5 0.542994723 6 7 0.546516121 8 0.551539336 9 0.571383505 10 0.573603603 11 0.578259633 12 Confidential: For Review Only 13 0.582424518 14 0.586664804 15 0.593098027 16 0.605224249 17 0.610879573 18 19 0.639182079 20 0.647257549 21 0.658849548 22 0.680319936 23 0.688876447 24 25 0.690202603 26 0.692806621 27 0.696581727 28 0.702479635 29 0.705135669 30 31 0.706890342 32 0.750423451 33 0.759791664 34 0.761641771 35 0.771183462 36 37 0.776826066 38 0.786351589 39 0.814628514 40 0.836253954 41 0.867118662 42 43 0.876197736 44 0.886607189 45 0.911819108 46 0.923011464 47 0.925555966 48 49 0.934936884 50 0.947256486 51 0.948333389 52 0.948565676 53 0.967308093 54 55 0.969187358 56 0.990302683 57 0.994017345 58 0.996218241 59 60

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1 2 Supplementary Table 5: Genome-wide association study results for early life body size in the UK Biobank (Females only) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs1421085 16 53800954 FTO T C 8 rs543874 1 177889480 SEC16B A G 9 rs6738433 2 25159501 DNAJC27 G C 10 rs62106258 2 417167 FAM150B T C 11 12 rs12992672 Confidential:2 632592ForTMEM18 ReviewG OnlyA 13 rs12042908 1 74997762 TNNI3K A G 14 rs7132908 12 50263148 FAIM2 G A 15 rs2168711 18 57848531 MC4R T C 16 rs12641981 4 45179883 GNPDA2 C T 17 18 rs148965598 16 19975731 GPR139 A G 19 rs34260097 6 100727703 SIM1 T G 20 rs2206277 6 50798526 TFAP2B C T 21 rs8030456 15 68076856 MAP2K5 C T 22 23 rs2126474 8 76878957 HNF4G G T 24 rs115319174 2 207066474 GPR1 G C 25 rs2531991 16 4023553 ADCY9 G A 26 rs10821163 9 96343060 PHF2 G C 27 rs11209943 1 72750500 NEGR1 A G 28 29 rs3131934 6 30931844 DPCR1 T C 30 rs2767486 1 65991203 LEPR A G 31 rs17066856 18 58049656 MC4R T C 32 rs34196306 6 27425644 ZNF184 G C 33 rs13254613 8 64804804 YTHDF3 A C 34 35 rs75782365 6 26408551 BTN3A1 T G 36 rs3749971 6 29342775 OR5V1 G A 37 rs11039307 11 47611152 C1QTNF4 C T 38 rs7084503 10 2666859 PFKP T C 39 rs7189927 16 28913787 ATP2A1 T C 40 41 rs75001243 7 93216002 GNGT1 C T 42 rs7377083 4 102708997 BANK1 C A 43 rs815610 5 153517178 MFAP3 C G 44 rs34229857 16 67434917 ZDHHC1 C T 45 rs9551428 13 28618462 FLT3 C T 46 47 rs10050620 5 63927239 RGS7BP C T 48 rs796915 6 154304628 OPRM1 C G 49 rs41279738 1 110082551 GPR61 T G 50 rs79569013 3 61218295 FHIT T G 51 rs4432271 16 20245283 GP2 C T 52 53 rs12110721 6 55190480 GFRAL G A 54 rs9268235 6 32290208 C6orf10 C T 55 rs2594989 3 11316143 ATG7 C T 56 rs61980008 14 30464716 PRKD1 G A 57 rs962369 11 27734420 BDNF T C 58 59 rs7268466 20 15810676 MACROD2 C T 60 rs7239114 18 45921214 ZBTB7C G A rs11215403 11 115058585 CADM1 G A

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1 2 rs1336486 13 40784814 AL133318.1 T G 3 rs11671304 19 47564643 ZC3H4 C T 4 rs9317002 13 59175727 PCDH17 C A 5 rs1775255 6 51243035 PKHD1 G T 6 7 rs11611246 12 939480 WNK1 G T 8 rs7656673 4 30840331 PCDH7 A G 9 rs1446725 2 77222421 LRRTM4 T G 10 rs818219 3 85374589 CADM2 T C 11 rs2303384 11 65640204 EFEMP2 C T 12 Confidential: For Review Only 13 rs2275241 9 129370576 LMX1B G A 14 rs6001872 22 40703245 TNRC6B A G 15 rs146910503 2 25446473 DNMT3A G A 16 rs76971642 10 87575243 GRID1 T C 17 rs4889630 16 30877544 BCL7C T C 18 19 rs4817972 21 40309591 ETS2 G C 20 rs66469746 20 54374063 CBLN4 C A 21 rs12214497 6 10015908 OFCC1 G T 22 rs9293494 5 87204121 TMEM161B T G 23 rs661878 11 29188691 METTL15 A G 24 25 rs818898 9 6970806 KDM4C A G 26 rs2034963 3 48170802 CDC25A G C 27 rs11642090 16 81730582 CMIP T C 28 rs10783302 12 49498130 LMBR1L G T 29 rs76152047 3 141183792 ZBTB38 A G 30 31 rs212540 1 21593117 ECE1 C T 32 rs1199328 3 138112107 MRAS G A 33 rs1349641 4 82212652 PRKG2 T G 34 rs62515439 8 57165417 CHCHD7 C T 35 rs3936511 5 55860781 AC022431.2 A G 36 37 rs994308 20 6603622 BMP2 C T 38 rs4235642 5 103818412 NUDT12 A G 39 rs1865719 14 79923667 NRXN3 A G 40 rs1483153 2 142358477 LRP1B C T 41 rs13233916 7 138874416 TTC26 C G 42 43 rs78607331 12 57648644 R3HDM2 C T 44 rs12334731 8 11098975 XKR6 G A 45 rs3810304 19 30861683 ZNF536 A G 46 rs2970356 15 90623540 ZNF710 C G 47 rs983949 7 24299013 NPY T G 48 49 rs10796828 11 69490346 ORAOV1 T G 50 rs4932430 15 89363866 ACAN A C 51 rs141127771 6 32632200 HLA-DQB1 G A 52 rs351776 8 28191306 PNOC A C 53 rs2735556 3 88105360 CGGBP1 T C 54 55 rs2187642 12 11855624 ETV6 A C 56 rs4477562 13 54104968 OLFM4 C T 57 rs62425122 6 166311987 PDE10A G A 58 rs7305424 12 118399491 KSR2 A T 59 rs582220 1 54724762 SSBP3 A G 60 rs12140153 1 62579891 INADL G T

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1 2 rs1576655 13 79587841 RBM26 A C 3 rs10798139 1 187714179 PLA2G4A C T 4 rs6979832 7 127856276 LEP A G 5 rs35202265 13 27986069 GTF3A C T 6 7 rs947088 20 17171373 PCSK2 G T 8 rs11150745 17 78757626 RPTOR A G 9 rs72755233 15 100692953 ADAMTS17 G A 10 rs7005216 8 8547110 CLDN23 G C 11 rs17464221 2 188278203 CALCRL C T 12 Confidential: For Review Only 13 rs4971239 1 203491150 OPTC G A 14 rs633372 19 49209226 FUT2 G A 15 rs10422861 19 33894846 PEPD C T 16 rs12185242 17 47407071 ZNF652 A C 17 rs2629881 3 59778271 FHIT C T 18 19 rs1546881 1 1660043 SLC35E2 T A 20 rs13190020 5 65012526 SGTB G A 21 rs3798544 6 34520267 SPDEF G A 22 rs9540493 13 66205704 PCDH9 A G 23 rs55959207 2 161016981 ITGB6 A C 24 25 rs7759938 6 105378954 LIN28B C T 26 rs957512 9 120405705 TLR4 T C 27 rs10784514 12 66452879 LLPH C T 28 rs1013737 18 937050 ADCYAP1 G C 29 rs303753 18 21074922 RIOK3 G A 30 31 rs7808296 7 103127620 RELN C T 32 rs999493 17 46625519 HOXB3 G A 33 rs536436655 1 196321444 KCNT2 A G 34 rs16982345 19 18500722 GDF15 G A 35 rs7562973 2 219471455 PLCD4 T C 36 37 rs2364232 12 93994827 SOCS2 A C 38 rs11863799 16 61933401 CDH8 C T 39 rs10876457 12 39453689 CPNE8 G A 40 rs12309017 12 99677307 ANKS1B G T 41 rs6860760 5 142868379 NR3C1 A G 42 43 rs242922 17 43946370 SPPL2C A C 44 rs12606230 18 52492252 RAB27B T C 45 rs815339 1 190116575 BRINP3 T A 46 rs7522014 1 66551759 PDE4B A G 47 rs76919525 12 50541733 CERS5 T A 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 5: Genome-wide association study results for early life2 body size in the UK Biobank (Females only) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.598576 -0.04853 0.00197394 1.70E-133 8 0.795036 -0.05476 0.00239487 1.00E-115 9 0.521298 -0.04046 0.00193814 8.80E-97 10 0.951237 0.087058 0.00448271 5.10E-84 11 12 0.171738Confidential:-0.04419 0.00255993 For9.00E-67 Review Only 13 0.437568 0.031664 0.00195106 3.10E-59 14 0.615703 -0.03132 0.00199033 8.40E-56 15 0.767084 -0.03547 0.00228473 2.30E-54 16 0.566316 -0.02326 0.00195503 1.20E-32 17 18 0.861328 0.032265 0.00282615 3.50E-30 19 0.776199 -0.02518 0.00231715 1.60E-27 20 0.820178 -0.02697 0.00252 1.00E-26 21 0.772735 0.023364 0.00230602 4.00E-24 22 23 0.585837 0.019639 0.00196722 1.80E-23 24 0.942615 -0.0412 0.00420209 1.10E-22 25 0.252908 -0.02011 0.00223338 2.20E-19 26 0.658856 -0.01843 0.00205361 2.80E-19 27 0.396665 -0.01749 0.0019728 7.50E-19 28 29 0.830748 -0.02277 0.00258089 1.10E-18 30 0.798051 -0.0203 0.00241094 3.80E-17 31 0.909035 0.028259 0.00337905 6.10E-17 32 0.893292 -0.0263 0.00315702 7.90E-17 33 0.653678 -0.01658 0.00203498 3.70E-16 34 35 0.892724 -0.02522 0.0031204 6.40E-16 36 0.878141 -0.02385 0.00295211 6.60E-16 37 0.590985 -0.01563 0.00196427 1.70E-15 38 0.4919 0.015426 0.00194201 2.00E-15 39 0.352011 0.015977 0.0020211 2.70E-15 40 41 0.639219 -0.0159 0.00201514 3.00E-15 42 0.570107 -0.01551 0.00196993 3.40E-15 43 0.442958 0.015188 0.00194806 6.40E-15 44 0.971245 -0.04457 0.00577952 1.20E-14 45 0.373637 0.015367 0.00200064 1.60E-14 46 47 0.674911 0.015865 0.00206889 1.70E-14 48 0.305503 -0.01603 0.00210384 2.50E-14 49 0.973821 -0.04633 0.00608129 2.60E-14 50 0.847448 0.020031 0.00268865 9.30E-14 51 0.131393 -0.0216 0.00291003 1.10E-13 52 53 0.825056 -0.0193 0.00261132 1.50E-13 54 0.868509 -0.0207 0.00280329 1.60E-13 55 0.178197 0.018587 0.0025339 2.20E-13 56 0.960939 -0.03657 0.00501195 3.00E-13 57 0.694195 -0.01528 0.0020985 3.30E-13 58 59 0.85579 -0.02011 0.00277572 4.40E-13 60 0.458018 -0.01415 0.00195718 4.80E-13 0.756934 0.016131 0.00225419 8.30E-13

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1 2 0.671032 -0.01474 0.00206196 8.80E-13 3 0.329036 -0.01473 0.00207363 1.20E-12 4 0.484805 -0.01383 0.00195001 1.30E-12 5 0.523256 -0.01365 0.00194006 2.00E-12 6 7 0.787302 -0.01655 0.00236412 2.50E-12 8 0.598244 -0.01372 0.00197211 3.50E-12 9 0.587024 0.013587 0.00196258 4.40E-12 10 0.540731 -0.01338 0.00194615 6.20E-12 11 0.358616 0.013805 0.00201341 7.10E-12 12 Confidential: For Review Only 13 0.628401 -0.01372 0.00200221 7.20E-12 14 0.65096 0.013914 0.00203341 7.80E-12 15 0.978739 0.046786 0.00693681 1.50E-11 16 0.952802 -0.03091 0.00458611 1.60E-11 17 0.200015 0.01621 0.00241762 2.00E-11 18 19 0.640508 0.013539 0.00201922 2.00E-11 20 0.714246 0.014375 0.00214919 2.30E-11 21 0.655579 0.013538 0.00203345 2.80E-11 22 0.764128 0.015147 0.00228236 3.20E-11 23 0.867001 0.01891 0.00284982 3.20E-11 24 25 0.31577 0.013927 0.00210323 3.60E-11 26 0.350909 0.013477 0.00204418 4.30E-11 27 0.626662 -0.01328 0.00201536 4.40E-11 28 0.63514 -0.0132 0.00200998 5.10E-11 29 0.933595 -0.02507 0.00390062 1.30E-10 30 31 0.392503 0.012688 0.00200134 2.30E-10 32 0.191322 0.015442 0.0024582 3.30E-10 33 0.602578 0.01246 0.00198207 3.30E-10 34 0.632779 0.012614 0.00200667 3.30E-10 35 0.80848 0.01537 0.00245863 4.10E-10 36 37 0.59559 -0.01232 0.00197326 4.30E-10 38 0.620775 0.012448 0.0019959 4.50E-10 39 0.367452 -0.01254 0.00201209 4.60E-10 40 0.219317 -0.01455 0.00233705 4.80E-10 41 0.910898 0.021095 0.00339421 5.10E-10 42 43 0.955142 -0.02894 0.00466796 5.60E-10 44 0.415531 0.012313 0.00199544 6.80E-10 45 0.225294 0.014297 0.00231895 7.00E-10 46 0.679219 -0.01335 0.00218787 1.10E-09 47 0.714774 -0.01305 0.00214576 1.20E-09 48 49 0.365278 -0.01224 0.0020136 1.20E-09 50 0.520603 0.011827 0.00195309 1.40E-09 51 0.740656 -0.01567 0.00260069 1.70E-09 52 0.452229 -0.01165 0.00194357 2.00E-09 53 0.885004 0.018112 0.0030224 2.10E-09 54 55 0.375754 -0.0119 0.00199449 2.40E-09 56 0.871693 -0.01721 0.00291642 3.60E-09 57 0.703489 0.012477 0.00211847 3.90E-09 58 0.657948 -0.01205 0.00204785 4.00E-09 59 0.433296 -0.01144 0.00195843 5.10E-09 60 0.906179 0.019845 0.00340164 5.40E-09

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1 2 0.40433 -0.01172 0.00201219 5.70E-09 3 0.783017 -0.0137 0.00235546 5.90E-09 4 0.503266 -0.01134 0.00194799 5.90E-09 5 0.377883 -0.01158 0.00200305 7.50E-09 6 7 0.281924 -0.01248 0.0021589 7.50E-09 8 0.681985 0.012037 0.00208311 7.60E-09 9 0.888484 -0.01774 0.00307255 7.80E-09 10 0.521898 0.01121 0.00194627 8.40E-09 11 0.710655 0.012303 0.00213709 8.60E-09 12 Confidential: For Review Only 13 0.831063 -0.01489 0.00260308 1.10E-08 14 0.466187 0.01108 0.00193749 1.10E-08 15 0.334244 -0.01168 0.00205468 1.30E-08 16 0.544476 -0.011 0.00194444 1.50E-08 17 0.221491 -0.01317 0.00233534 1.70E-08 18 19 0.627849 -0.0126 0.00223933 1.80E-08 20 0.65376 -0.01146 0.00203426 1.80E-08 21 0.866888 -0.01611 0.00286034 1.80E-08 22 0.453952 0.011 0.00195452 1.80E-08 23 0.573522 0.010949 0.00194913 1.90E-08 24 25 0.321596 -0.01163 0.00207287 2.00E-08 26 0.669346 0.011564 0.00206134 2.00E-08 27 0.31988 -0.01162 0.00207375 2.10E-08 28 0.506587 -0.01086 0.00193947 2.10E-08 29 0.654846 -0.01151 0.00205191 2.10E-08 30 31 0.685093 -0.01165 0.00208172 2.20E-08 32 0.377882 -0.0112 0.00200527 2.30E-08 33 0.931672 -0.02136 0.00384778 2.80E-08 34 0.749552 -0.01242 0.00223762 2.80E-08 35 0.594729 -0.01102 0.00198743 2.90E-08 36 37 0.740504 0.012276 0.00221272 2.90E-08 38 0.675113 0.01145 0.00206543 3.00E-08 39 0.774673 0.012833 0.00232411 3.40E-08 40 0.746762 -0.01238 0.00224399 3.50E-08 41 0.43438 0.010762 0.00195494 3.70E-08 42 43 0.405892 -0.01109 0.00201479 3.70E-08 44 0.766539 -0.01258 0.00229058 4.00E-08 45 0.49499 -0.01065 0.00194161 4.20E-08 46 0.672706 0.011472 0.00209979 4.70E-08 47 0.341868 -0.01134 0.00207823 4.90E-08 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 6: Genome-wide association study results for adulthood body size in the UK Biobank (Females only) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs56094641 16 53806453 FTO A G 8 rs66922415 18 57848651 MC4R A G 9 rs539515 1 177889025 SEC16B A C 10 rs62106258 2 417167 FAM150B T C 11 12 rs6548237 Confidential:2 621461ForTMEM18 ReviewA Only C 13 rs6749422 2 25150011 ADCY3 C G 14 rs2103646 6 34571195 C6orf106 G A 15 rs1013402 11 27712381 BDNF A G 16 rs72892910 6 50816887 TFAP2B G T 17 18 rs34341 5 74934009 ANKDD1B A T 19 rs34898535 16 31025641 STX1B C T 20 rs7132908 12 50263148 FAIM2 G A 21 rs1800437 19 46181392 GIPR G C 22 23 rs62031562 16 28609329 SULT1A2 A T 24 rs9843653 3 49920571 MST1R T C 25 rs879620 16 4015729 ADCY9 C T 26 rs12641981 4 45179883 GNPDA2 C T 27 rs34811474 4 25408838 ANAPC4 G A 28 29 rs34517439 1 78450517 DNAJB4 C A 30 rs4776985 15 68123021 SKOR1 T G 31 rs17066856 18 58049656 MC4R T C 32 rs113211479 11 47669861 MTCH2 G A 33 rs60572790 11 43692383 HSD17B12 T C 34 35 rs1270799 10 21907423 MLLT10 T G 36 rs13107325 4 103188709 SLC39A8 C T 37 rs8049669 16 69551467 NFAT5 A T 38 rs17770336 9 28414625 LINGO2 C T 39 rs11691869 2 100805996 AFF3 C A 40 41 rs3814883 16 29994922 TAOK2 C T 42 rs3803005 12 123110654 KNTC1 T C 43 rs288187 5 107344426 FBXL17 C T 44 rs13292699 9 15910044 CCDC171 A C 45 rs11074452 16 20370168 PDILT C G 46 47 rs10957605 8 73433886 KCNB2 C T 48 rs12357890 10 99762693 CRTAC1 A G 49 rs13416992 2 59298298 FANCL A C 50 rs17716502 8 116659731 TRPS1 C T 51 rs3130048 6 31613739 BAG6 T C 52 53 rs3810291 19 47569003 ZC3H4 G A 54 rs236660 7 75050086 POM121C T C 55 rs61813324 1 156049877 MEX3A C T 56 rs400997 21 46564154 ADARB1 T A 57 rs6575340 14 94023972 UNC79 G A 58 59 rs7442885 5 87682877 TMEM161B C G 60 rs7200589 16 349331 AXIN1 G A rs10404726 19 18834514 CRTC1 C T

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1 2 rs10514963 5 63027870 HTR1A G A 3 rs7950166 11 8642218 TRIM66 C T 4 rs4671328 2 58935282 FANCL T G 5 rs34298980 6 40409243 LRFN2 T C 6 7 rs8022132 14 79955864 NRXN3 A T 8 rs10922911 1 91205831 BARHL2 C T 9 rs73052033 3 185828465 DGKG T C 10 rs7602120 2 144033069 ARHGAP15 C T 11 rs11150745 17 78757626 RPTOR A G 12 Confidential: For Review Only 13 rs34292685 11 64049021 GPR137 C T 14 rs13174863 5 139080745 CXXC5 A G 15 rs769668 4 140858717 MAML3 T C 16 rs1514173 1 74995110 TNNI3K C T 17 rs2815757 1 72764289 NEGR1 C T 18 19 rs770082 12 89776485 DUSP6 G A 20 rs73213484 4 28489339 RP11-180C1.1 A T 21 rs2994320 1 243641247 SDCCAG8 A G 22 rs815163 1 190294726 BRINP3 T C 23 rs11022766 11 13348249 ARNTL T G 24 25 rs78886584 1 16859325 FAM231B A G 26 rs41279738 1 110082551 GPR61 T G 27 rs113585475 10 33985434 NRP1 C T 28 rs10896012 11 65278461 SCYL1 T C 29 rs12866691 13 58623783 PCDH17 A T 30 31 rs75641275 1 98327133 DPYD A C 32 rs7090758 10 65335315 REEP3 T C 33 rs12986231 19 18469017 PGPEP1 T C 34 rs34966255 20 51193862 ZFP64 T C 35 rs9568867 13 54107352 OLFM4 G A 36 37 rs2678204 1 201800511 IPO9 T G 38 rs3952972 3 131771282 CPNE4 T C 39 rs75104958 14 33269269 AKAP6 A C 40 rs429358 19 45411941 APOE T C 41 rs9579775 13 20616557 ZMYM2 A C 42 43 rs12891477 14 104332759 PPP1R13B C T 44 rs13262807 8 77224826 ZFHX4 A G 45 rs4790292 17 1824305 RTN4RL1 C A 46 rs28722029 22 40611012 TNRC6B G A 47 rs3751859 16 81735012 CMIP G A 48 49 rs11660335 18 22154235 HRH4 T C 50 rs2512884 11 131467856 NTM C A 51 rs4527444 4 30842780 PCDH7 A G 52 rs1454687 3 94038085 NSUN3 C G 53 rs2035936 3 141298124 RASA2 G T 54 55 rs939624 15 99480551 IGF1R C T 56 rs61217499 12 108417780 WSCD2 G C 57 rs12974664 19 1856186 KLF16 G A 58 rs143779385 14 29818782 PRKD1 T A 59 rs8124896 20 21385659 NKX2-4 T C 60 rs1914889 17 21267590 KCNJ12 G A

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1 2 rs11134679 5 170623391 RANBP17 A G 3 rs139313721 3 61193925 FHIT A G 4 rs11250094 8 10802001 XKR6 G C 5 rs3802858 11 115078492 CADM1 T C 6 7 rs13081671 3 135876549 MSL2 C T 8 rs1840661 7 114352682 FOXP2 T A 9 rs2292238 12 56493822 ERBB3 A C 10 rs55726687 12 991306 WNK1 G A 11 rs7853 8 8890814 ERI1 A G 12 Confidential: For Review Only 13 rs1477290 5 87988934 MEF2C T C 14 rs1494461 1 49787196 AGBL4 C T 15 rs116948922 20 25534854 NINL C T 16 rs11079849 17 47090785 IGF2BP1 C T 17 rs11098965 4 80888040 ANTXR2 C T 18 19 rs111640872 19 30290357 CCNE1 G C 20 rs12033257 1 112318484 KCND3 A G 21 rs12467692 2 181566711 UBE2E3 G A 22 rs6545468 2 55277641 RTN4 C G 23 rs1576655 13 79587841 RBM26 A C 24 25 rs3953834 2 104343485 TMEM182 T A 26 rs12477088 2 67841326 ETAA1 T C 27 rs4673553 2 211608379 CPS1 T G 28 rs2396625 7 113028634 TSRM T A 29 rs891386 18 21103971 NPC1 T G 30 31 rs13066308 3 82713150 GBE1 C G 32 rs4482463 2 205375909 PARD3B C A 33 rs7047694 9 103141037 TEX10 G A 34 rs4148155 4 89054667 ABCG2 A G 35 rs529200 3 173114305 NLGN1 A G 36 37 rs181617194 12 122011598 KDM2B T C 38 rs77706698 17 65953348 BPTF G A 39 rs12144626 1 47670525 TAL1 T C 40 rs13420048 2 50751414 NRXN1 C A 41 rs9395520 6 13183523 PHACTR1 C T 42 43 rs200570844 5 153105920 GRIA1 A T 44 rs148712344 4 55476318 KIT G T 45 rs2619976 17 71754545 SDK2 C T 46 rs12375196 7 103416541 RELN C A 47 rs73046311 7 1854159 MAD1L1 C G 48 49 rs7145882 14 103255461 TRAF3 T C 50 rs17399739 10 87490850 GRID1 A G 51 rs2253310 6 108888593 FOXO3 C G 52 rs7976757 12 19207948 PLEKHA5 T C 53 rs350832 19 4069426 ZBTB7A G A 54 55 rs10510025 10 118650996 KIAA1598 C T 56 rs6557829 8 21973970 HR C A 57 rs2866720 7 70106310 AUTS2 C T 58 rs191621046 5 92547517 NR2F1 G A 59 rs2306593 17 34866546 MYO19 C T 60 rs13329943 16 24733751 TNRC6A C T

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1 2 rs2398851 9 96398508 PHF2 A G 3 rs10038055 5 88783421 MEF2C G T 4 rs9387640 6 119508871 MAN1A1 C T 5 rs11146233 10 134000962 DPYSL4 G A 6 7 rs67962220 15 74188926 TBC1D21 T G 8 rs111828690 12 117576767 FBXO21 C T 9 rs113706999 3 44159156 TOPAZ1 T A 10 rs11223204 11 132652554 OPCML A G 11 rs251353 5 140228164 PCDHA1 C A 12 Confidential: For Review Only 13 rs34606703 2 47014522 SOCS5 G A 14 rs653958 1 96884006 PTBP2 A G 15 rs72906474 3 47817007 SMARCC1 G T 16 rs1933440 13 28676971 FLT3 A C 17 rs201168005 6 98584713 POU3F2 T A 18 19 rs7752998 6 34398358 RPS10 A T 20 rs116394958 13 86477072 SLITRK6 C T 21 rs715724 15 80984293 ABHD17C A G 22 rs828550 5 3539923 IRX1 C T 23 rs915814 21 46493003 AP001579.1 G A 24 25 rs10849900 12 110974890 PPTC7 T C 26 rs1547026 6 51825622 PKHD1 T C 27 rs10142359 14 73884540 NUMB A G 28 rs29028878 6 29911727 HLA-A T C 29 rs791405 8 64720735 YTHDF3 T C 30 31 rs1250535 10 81016112 ZMIZ1 C G 32 rs3003578 9 130994179 DNM1 C T 33 rs35778344 6 28599105 SCAND3 G A 34 rs738140 22 41884954 ACO2 A G 35 rs1466276 15 52025950 LYSMD2 C G 36 37 rs74892851 1 1563789 MIB2 C A 38 rs117176448 8 27261138 PTK2B C G 39 rs4962725 10 126733321 CTBP2 T C 40 rs1083472 2 147873492 ACVR2A C G 41 rs12140153 1 62579891 INADL G T 42 43 rs2433733 2 230816703 FBXO36 G A 44 rs62242071 3 20590313 SGOL1 G T 45 rs35390852 4 143067054 INPP4B G A 46 rs59893724 5 80830788 SSBP2 A G 47 rs10192894 2 62838936 EHBP1 A G 48 49 rs567230078 6 43588227 GTPBP2 T A 50 rs4740442 9 10153245 PTPRD C T 51 rs925422 4 60254101 LPHN3 T G 52 rs11976018 7 99122437 ZKSCAN5 G A 53 rs6774533 3 62471086 CADPS C T 54 55 rs11218510 11 121922587 BLID G A 56 rs12364470 11 134601012 AP003062.1 T G 57 rs1603179 4 67805347 CENPC A C 58 rs784257 18 53397199 TCF4 T C 59 rs2761366 13 33011872 N4BP2L2 C T 60 rs72660086 1 39571992 MACF1 T G

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1 2 rs77253887 6 35626932 FKBP5 G C 3 rs3753639 1 154986091 ZBTB7B T C 4 rs57790054 16 20006986 GPR139 A G 5 rs777676 9 129691913 RALGPS1 T A 6 7 rs9684942 4 20233035 SLIT2 G A 8 rs56212061 19 19394640 SUGP1 C T 9 rs9811252 3 128293392 C3orf27 C T 10 rs11000942 10 76025256 ADK G A 11 rs57590313 4 113323430 ALPK1 C A 12 Confidential: For Review Only 13 rs12971645 19 45807945 MARK4 G A 14 rs9522180 13 111970212 TEX29 C T 15 rs2643450 4 18547417 LCORL A G 16 rs6478538 9 124627012 TTLL11 A G 17 rs9962947 18 72903636 ZADH2 C T 18 19 rs1366334 5 122683163 CEP120 C G 20 rs3125326 10 63053788 TMEM26 A C 21 rs61218008 3 194881130 XXYLT1 A G 22 rs11880064 19 33964181 PEPD T C 23 rs7331420 13 99236471 STK24 G A 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 6: Genome-wide association study results for adulthood2 body size in the UK Biobank (Females only) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.59742 -0.04558 0.00200785 4.30E-114 8 0.767172 -0.03858 0.0023249 7.40E-62 9 0.79533 -0.03759 0.0024354 9.60E-54 10 0.951237 0.067317 0.00455471 2.00E-49 11 12 0.173288Confidential:-0.03615 0.00259262 For3.40E-44 Review Only 13 0.514415 -0.02413 0.00196602 1.20E-34 14 0.671261 -0.0223 0.00209544 1.90E-26 15 0.68069 -0.02127 0.0021076 6.00E-24 16 0.827643 -0.02619 0.00260784 9.70E-24 17 18 0.42517 -0.01998 0.00199076 1.10E-23 19 0.623021 0.01922 0.0020298 2.80E-21 20 0.615703 -0.01895 0.00202542 8.20E-21 21 0.805416 0.023047 0.00248535 1.80E-20 22 23 0.625507 -0.01847 0.00203882 1.30E-19 24 0.489638 -0.01758 0.00196762 4.20E-19 25 0.386937 -0.01739 0.00202757 9.70E-18 26 0.566316 -0.01681 0.00198795 2.80E-17 27 0.769584 0.019703 0.00233505 3.20E-17 28 29 0.877703 -0.02525 0.00303342 8.40E-17 30 0.774241 0.019572 0.00235276 8.90E-17 31 0.909035 0.028109 0.0034379 2.90E-16 32 0.595599 -0.01562 0.00200217 6.10E-15 33 0.681159 -0.01652 0.0021237 7.20E-15 34 35 0.696226 -0.01653 0.00214151 1.20E-14 36 0.926018 -0.02879 0.00375909 1.90E-14 37 0.43052 0.015508 0.00203065 2.20E-14 38 0.676459 -0.01603 0.00210294 2.50E-14 39 0.637193 0.015537 0.00204782 3.30E-14 40 41 0.517332 -0.01498 0.00197608 3.50E-14 42 0.269836 -0.01681 0.00221952 3.60E-14 43 0.827122 0.019809 0.00261975 4.00E-14 44 0.567036 0.015023 0.00198955 4.30E-14 45 0.491808 0.014713 0.00197083 8.30E-14 46 47 0.317896 0.015787 0.00212097 9.80E-14 48 0.443397 -0.01477 0.00199097 1.20E-13 49 0.396024 0.014785 0.00201023 1.90E-13 50 0.795263 0.017884 0.0024585 3.50E-13 51 0.720376 -0.01582 0.00218591 4.60E-13 52 53 0.324288 -0.01521 0.00210317 4.70E-13 54 0.429762 -0.01489 0.00206335 5.40E-13 55 0.864564 -0.02089 0.00291412 7.60E-13 56 0.440649 -0.0143 0.00199775 8.00E-13 57 0.364843 -0.01459 0.00205106 1.10E-12 58 59 0.786359 0.016992 0.00240321 1.50E-12 60 0.727338 0.015598 0.00221757 2.00E-12 0.534319 0.013847 0.00197647 2.50E-12

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1 2 0.519165 -0.01372 0.00196677 3.00E-12 3 0.354353 -0.01435 0.00205708 3.00E-12 4 0.447948 0.013654 0.00198781 6.50E-12 5 0.492074 0.014147 0.00207298 8.80E-12 6 7 0.697301 -0.01461 0.00214725 1.00E-11 8 0.628826 -0.01383 0.00203706 1.10E-11 9 0.815273 0.017216 0.00253661 1.10E-11 10 0.53433 -0.01341 0.00197733 1.20E-11 11 0.681985 0.014302 0.00211971 1.50E-11 12 Confidential: For Review Only 13 0.838675 0.017997 0.00267116 1.60E-11 14 0.852203 -0.01872 0.00278686 1.80E-11 15 0.653161 0.013957 0.00207711 1.80E-11 16 0.597973 -0.01344 0.00200283 1.90E-11 17 0.191393 -0.01671 0.00249264 2.00E-11 18 19 0.562727 -0.01336 0.00199481 2.10E-11 20 0.858475 0.018902 0.00282767 2.30E-11 21 0.804332 0.016622 0.00248828 2.40E-11 22 0.43793 0.01322 0.00197884 2.40E-11 23 0.640911 0.013803 0.00206875 2.50E-11 24 25 0.508707 -0.01327 0.00199026 2.60E-11 26 0.973821 -0.04097 0.00618096 3.40E-11 27 0.900241 0.022 0.00332265 3.60E-11 28 0.783646 -0.01583 0.00239359 3.70E-11 29 0.772619 0.015518 0.00234792 3.90E-11 30 31 0.857289 -0.01849 0.00280998 4.70E-11 32 0.526046 -0.01293 0.0019731 5.70E-11 33 0.731611 0.014685 0.00224574 6.20E-11 34 0.807515 0.016399 0.00250768 6.20E-11 35 0.871146 -0.01932 0.00296096 6.80E-11 36 37 0.659227 -0.01336 0.00207341 1.20E-10 38 0.681403 -0.01359 0.00211311 1.30E-10 39 0.744243 -0.01574 0.00244788 1.30E-10 40 0.84577 0.017504 0.00272945 1.40E-10 41 0.864084 -0.01917 0.00298802 1.40E-10 42 43 0.630988 -0.01308 0.00205087 1.80E-10 44 0.507322 -0.01331 0.00208535 1.80E-10 45 0.845933 0.017458 0.00273693 1.80E-10 46 0.677715 0.013427 0.00211575 2.20E-10 47 0.843232 0.017141 0.00270548 2.40E-10 48 49 0.809841 0.015916 0.00251614 2.50E-10 50 0.484094 -0.01241 0.00197509 3.30E-10 51 0.458064 -0.01241 0.001975 3.30E-10 52 0.484383 0.012292 0.00196612 4.10E-10 53 0.943923 -0.02703 0.0043327 4.40E-10 54 55 0.538047 -0.01231 0.0019769 4.70E-10 56 0.780075 0.01485 0.00239579 5.70E-10 57 0.464349 -0.01228 0.00198455 6.00E-10 58 0.804957 -0.01544 0.00250236 6.90E-10 59 0.898608 -0.02014 0.00326593 6.90E-10 60 0.546799 0.0122 0.00198428 7.80E-10

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1 2 0.314617 -0.01307 0.00212759 8.00E-10 3 0.584723 0.012212 0.00200002 1.00E-09 4 0.4528 0.012082 0.00198174 1.10E-09 5 0.572753 0.012107 0.00198713 1.10E-09 6 7 0.728006 -0.01347 0.00221718 1.20E-09 8 0.574859 -0.01216 0.00199896 1.20E-09 9 0.593477 0.012178 0.0020052 1.30E-09 10 0.789106 -0.01462 0.00241144 1.30E-09 11 0.552779 -0.01203 0.00198059 1.30E-09 12 Confidential: For Review Only 13 0.863249 -0.01749 0.0028886 1.40E-09 14 0.320689 0.012736 0.00210245 1.40E-09 15 0.967422 0.03396 0.00561587 1.50E-09 16 0.670897 0.012664 0.00209949 1.60E-09 17 0.292525 0.013621 0.0022577 1.60E-09 18 19 0.66931 -0.01264 0.00210035 1.80E-09 20 0.61783 0.012243 0.0020378 1.90E-09 21 0.368907 -0.01239 0.00206905 2.10E-09 22 0.587241 0.011981 0.00200202 2.20E-09 23 0.40433 -0.01222 0.00204713 2.40E-09 24 25 0.532581 0.011822 0.00198482 2.60E-09 26 0.589504 0.011861 0.00199436 2.70E-09 27 0.552077 -0.01172 0.00197918 3.20E-09 28 0.577887 0.011835 0.00200247 3.40E-09 29 0.541759 0.011664 0.00197324 3.40E-09 30 31 0.63852 -0.01206 0.00204403 3.70E-09 32 0.0769045 0.021784 0.00369502 3.70E-09 33 0.680805 -0.01245 0.00211155 3.70E-09 34 0.887078 0.018277 0.00310275 3.80E-09 35 0.473194 -0.0116 0.00197146 4.00E-09 36 37 0.958529 0.031674 0.00539031 4.20E-09 38 0.867613 -0.01716 0.00291934 4.20E-09 39 0.417175 0.011716 0.00199667 4.40E-09 40 0.634786 0.011999 0.00204443 4.40E-09 41 0.695088 0.012536 0.00213848 4.60E-09 42 43 0.559553 0.01159 0.00197809 4.70E-09 44 0.960382 0.029824 0.00510381 5.10E-09 45 0.586832 -0.01173 0.00201003 5.40E-09 46 0.575855 -0.0117 0.00200538 5.50E-09 47 0.838741 0.015674 0.0026912 5.70E-09 48 49 0.341919 0.012068 0.00207504 6.00E-09 50 0.931099 -0.02262 0.00389209 6.10E-09 51 0.373937 -0.01181 0.00203205 6.10E-09 52 0.172576 -0.01521 0.00261585 6.10E-09 53 0.22899 -0.0137 0.00236023 6.50E-09 54 55 0.753022 -0.01326 0.00228816 6.90E-09 56 0.594882 -0.01161 0.00200423 6.90E-09 57 0.614797 -0.01179 0.00203561 7.00E-09 58 0.961875 -0.02978 0.00514509 7.10E-09 59 0.510143 0.011415 0.00197286 7.20E-09 60 0.269427 -0.01284 0.00222447 7.90E-09

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1 2 0.319538 0.012224 0.00211892 8.00E-09 3 0.632408 -0.01181 0.00204946 8.30E-09 4 0.637026 0.011752 0.00204536 9.20E-09 5 0.438591 0.011397 0.00198521 9.40E-09 6 7 0.830923 -0.01507 0.00262744 9.80E-09 8 0.779209 -0.01368 0.00238799 1.00E-08 9 0.976417 -0.03871 0.00676328 1.00E-08 10 0.565064 -0.01135 0.00198868 1.10E-08 11 0.471203 0.011852 0.0020718 1.10E-08 12 Confidential: For Review Only 13 0.641616 0.011743 0.00205583 1.10E-08 14 0.629206 -0.01164 0.0020362 1.10E-08 15 0.415872 0.011541 0.00201884 1.10E-08 16 0.836783 -0.01534 0.0026895 1.20E-08 17 0.517396 0.011251 0.00197256 1.20E-08 18 19 0.206678 0.014257 0.00250955 1.30E-08 20 0.726128 -0.01257 0.0022128 1.40E-08 21 0.649404 0.0117 0.00206433 1.40E-08 22 0.355474 -0.01173 0.00207282 1.50E-08 23 0.76138 0.013082 0.00231276 1.50E-08 24 25 0.689661 0.012032 0.00213036 1.60E-08 26 0.708767 -0.01233 0.0021828 1.60E-08 27 0.518236 -0.01112 0.00197225 1.70E-08 28 0.535591 0.012591 0.00223121 1.70E-08 29 0.533418 0.011294 0.00200113 1.70E-08 30 31 0.324727 -0.01187 0.00211052 1.80E-08 32 0.44127 0.011246 0.00199662 1.80E-08 33 0.803234 -0.01393 0.00247182 1.80E-08 34 0.689026 0.011998 0.0021319 1.80E-08 35 0.524253 0.011134 0.00198088 1.90E-08 36 37 0.622756 0.011586 0.00205969 1.90E-08 38 0.903964 -0.01874 0.00333723 2.00E-08 39 0.571767 -0.01117 0.00199125 2.00E-08 40 0.386033 0.011326 0.00202146 2.10E-08 41 0.906179 0.019311 0.00345739 2.30E-08 42 43 0.321661 0.011736 0.00210148 2.30E-08 44 0.669069 0.011794 0.00211143 2.30E-08 45 0.876095 -0.01669 0.00299312 2.40E-08 46 0.755843 0.012787 0.00229268 2.40E-08 47 0.561654 -0.01103 0.00197929 2.50E-08 48 49 0.973122 0.033972 0.00609444 2.50E-08 50 0.714873 -0.01215 0.00218384 2.60E-08 51 0.257345 0.012538 0.00225639 2.70E-08 52 0.846011 0.015133 0.00272597 2.80E-08 53 0.295771 -0.01218 0.00219499 2.80E-08 54 55 0.599238 0.011176 0.00201372 2.90E-08 56 0.83592 -0.01473 0.00265569 2.90E-08 57 0.355894 0.011425 0.00205932 2.90E-08 58 0.187649 -0.01407 0.00253477 2.90E-08 59 0.358209 -0.01137 0.00205674 3.20E-08 60 0.788737 -0.01334 0.00241047 3.20E-08

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1 2 0.956562 -0.03029 0.00549417 3.50E-08 3 0.755881 -0.01264 0.00229716 3.70E-08 4 0.739079 -0.01236 0.00224576 3.70E-08 5 0.510935 0.010871 0.00197503 3.70E-08 6 7 0.852964 -0.01535 0.00279041 3.80E-08 8 0.849014 0.01517 0.00275964 3.90E-08 9 0.609011 0.011351 0.00206601 3.90E-08 10 0.876421 -0.01638 0.00298347 4.00E-08 11 0.807154 -0.01407 0.00256599 4.10E-08 12 Confidential: For Review Only 13 0.724983 0.012137 0.00221517 4.30E-08 14 0.447299 0.010849 0.0019823 4.40E-08 15 0.459307 -0.0108 0.00197447 4.50E-08 16 0.323309 0.011504 0.00210469 4.60E-08 17 0.362028 -0.0112 0.00204898 4.60E-08 18 19 0.292733 0.011828 0.00216525 4.70E-08 20 0.391436 -0.01113 0.00203818 4.70E-08 21 0.721236 0.012071 0.00220924 4.70E-08 22 0.636186 -0.01119 0.00205035 4.80E-08 23 0.714897 0.01195 0.00218879 4.80E-08 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 7: Genome-wide association study results for early life body size in the UK Biobank (Males only) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs56094641 16 53806453 FTO A G 8 rs374892365 2 633055 TMEM18 A T 9 rs539515 1 177889025 SEC16B A C 10 rs6749422 2 25150011 ADCY3 C G 11 12 rs7132908 Confidential:12 50263148 ForFAIM2 ReviewG OnlyA 13 rs77165542 2 430975 FAM150B C T 14 rs663129 18 57838401 MC4R G A 15 rs4650277 1 74993721 TNNI3K A G 16 rs10938398 4 45186139 GNPDA2 G A 17 18 rs7190603 16 19928662 GPRC5B T C 19 rs115319174 2 207066474 GPR1 G C 20 rs2012697 1 72819612 NEGR1 T C 21 rs62405422 6 50796905 TFAP2B T C 22 23 rs9568868 13 54107583 OLFM4 G T 24 rs3784710 15 68072458 MAP2K5 T C 25 rs7550711 1 110082886 GPR61 C T 26 rs11030102 11 27681596 BDNF C G 27 rs2540031 16 4017567 ADCY9 T A 28 29 rs1532127 19 47571938 ZC3H4 G A 30 rs41310284 10 102447647 PAX2 C A 31 rs9438393 1 205782718 SLC41A1 A G 32 rs10504620 8 77288303 ZFHX4 T C 33 rs10968101 9 27772542 LINGO2 G A 34 35 rs115597956 6 54042871 MLIP G A 36 rs12110721 6 55190480 GFRAL G A 37 rs12140153 1 62579891 INADL G T 38 rs3817334 11 47650993 MTCH2 C T 39 rs1775255 6 51243035 PKHD1 G T 40 41 rs13240802 7 76631109 UPK3B G A 42 rs1412815 13 66208985 PCDH9 A T 43 rs78444298 1 184672098 EDEM3 G A 44 rs10496885 2 142285767 LRP1B G A 45 rs75577466 5 60605507 ZSWIM6 G C 46 47 rs7316962 13 28613993 FLT3 A G 48 rs1321434 20 6624443 BMP2 A G 49 rs7978659 12 49507127 LMBR1L G T 50 rs7239114 18 45921214 ZBTB7C G A 51 rs3927084 16 28639047 SULT1A1 A C 52 53 rs12452089 17 2135002 SMG6 A T 54 rs7306710 12 66376091 HMGA2 T C 55 rs2143975 14 33297398 AKAP6 C G 56 rs73898513 20 15806210 MACROD2 C T 57 rs11790060 9 96202932 FAM120AOS T C 58 59 rs4958361 5 153545587 MFAP3 C G 60 rs2979139 8 8268313 SGK223 A G rs25842 5 66163135 MAST4 C T

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1 2 rs17637472 17 47461433 RP11-81K2.1 G A 3 rs13107325 4 103188709 SLC39A8 C T 4 rs10896348 11 68357368 PPP6R3 T C 5 rs9269212 6 32450249 HLA-DRB5 T A 6 7 rs9880272 3 85687785 CADM2 T G 8 rs2862874 2 58990485 FANCL G T 9 rs61978655 14 30491807 PRKD1 G A 10 rs55654862 5 77428253 AP3B1 A G 11 rs16119 7 24334930 NPY A G 12 Confidential: For Review Only 13 rs1452991 6 141473363 NMBR G A 14 rs12674871 8 9979144 MSRA C T 15 rs2250081 17 74090700 EXOC7 G A 16 rs2910977 5 52346049 ITGA2 C T 17 rs2240071 6 30070932 TRIM31 C G 18 19 rs7796922 7 33171110 BBS9 A G 20 rs3764516 18 52494374 RAB27B A C 21 rs11218734 11 122523246 UBASH3B A G 22 rs7159126 14 93783176 BTBD7 T C 23 rs4688359 3 61198880 FHIT C T 24 25 rs13132853 4 38680015 KLF3 A G 26 rs1576655 13 79587841 RBM26 A C 27 rs2693560 6 117523671 VGLL2 A G 28 rs545433658 7 140654203 BRAF G A 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 7: Genome-wide association study results for early 2life body size in the UK Biobank (Males only) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body3 size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.592926 -0.04626 0.00208809 9.10E-109 8 0.172138 -0.04236 0.00272836 2.30E-54 9 0.794706 -0.03878 0.00253888 1.20E-52 10 0.513756 -0.0313 0.00205062 1.30E-52 11 12 Confidential:0.61534 -0.03173 0.00210877 For3.70E-51 Review Only 13 0.964633 0.07292 0.00562542 2.00E-38 14 0.766362 -0.03059 0.00242937 2.40E-36 15 0.434972 0.022545 0.00206779 1.10E-27 16 0.564934 -0.02079 0.00207646 1.30E-23 17 18 0.858283 0.029517 0.00294663 1.30E-23 19 0.942157 -0.04348 0.00444282 1.30E-22 20 0.40094 -0.01919 0.00208947 4.20E-20 21 0.820351 -0.02187 0.00267432 2.90E-16 22 23 0.870238 -0.02485 0.00308111 7.40E-16 24 0.774324 0.019139 0.00244792 5.40E-15 25 0.974201 -0.05066 0.00649247 6.10E-15 26 0.740105 -0.01769 0.00233924 3.90E-14 27 0.404794 -0.01574 0.00213605 1.70E-13 28 29 0.317824 -0.01566 0.00220343 1.20E-12 30 0.899122 0.024153 0.00343726 2.10E-12 31 0.586344 0.01462 0.00208369 2.30E-12 32 0.30137 -0.01518 0.00224009 1.20E-11 33 0.522489 -0.01376 0.00205912 2.30E-11 34 35 0.945374 -0.02994 0.00451933 3.50E-11 36 0.826289 -0.01824 0.00278115 5.40E-11 37 0.905264 0.02345 0.00358598 6.20E-11 38 0.59283 -0.0136 0.00208252 6.60E-11 39 0.523597 -0.01332 0.00206005 1.00E-10 40 41 0.249069 0.016513 0.00261481 2.70E-10 42 0.394462 0.01333 0.00211409 2.90E-10 43 0.980678 0.047223 0.00750671 3.20E-10 44 0.813737 0.016564 0.00263593 3.30E-10 45 0.822678 0.016939 0.00270047 3.50E-10 46 47 0.453454 0.012929 0.00206357 3.70E-10 48 0.540081 -0.01278 0.0020592 5.40E-10 49 0.657854 -0.01335 0.00216331 6.90E-10 50 0.458743 -0.01276 0.00207672 8.00E-10 51 0.590581 -0.01256 0.00208792 1.80E-09 52 53 0.650315 0.012965 0.00215524 1.80E-09 54 0.478843 0.012407 0.00206902 2.00E-09 55 0.466424 0.012266 0.00207064 3.10E-09 56 0.877529 -0.01875 0.0031825 3.80E-09 57 0.669266 -0.01285 0.00218269 3.90E-09 58 59 0.47209 0.012066 0.00205413 4.30E-09 60 0.507064 -0.01208 0.00205766 4.30E-09 0.722624 0.013439 0.00229862 5.00E-09

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1 2 0.602276 -0.01238 0.00211769 5.00E-09 3 0.924027 -0.02266 0.00387926 5.20E-09 4 0.723406 0.01335 0.00228818 5.40E-09 5 0.754059 -0.01433 0.00248601 8.10E-09 6 7 0.758575 -0.01382 0.00239777 8.20E-09 8 0.38849 -0.01208 0.00211384 1.10E-08 9 0.961487 -0.03043 0.00535136 1.30E-08 10 0.762977 0.013671 0.00241139 1.40E-08 11 0.480301 0.011643 0.00205811 1.50E-08 12 Confidential: For Review Only 13 0.627381 -0.01209 0.00213953 1.60E-08 14 0.799049 -0.01439 0.00256879 2.10E-08 15 0.552294 0.011503 0.00206559 2.60E-08 16 0.930465 0.022491 0.00404707 2.70E-08 17 0.746927 -0.01311 0.00236119 2.80E-08 18 19 0.906001 0.019574 0.00353102 3.00E-08 20 0.234545 0.013393 0.00242498 3.30E-08 21 0.742952 -0.01295 0.00234659 3.40E-08 22 0.717605 0.012567 0.00228019 3.60E-08 23 0.625376 0.011683 0.00212299 3.70E-08 24 25 0.639582 0.011812 0.00214767 3.80E-08 26 0.403779 -0.01176 0.00213722 3.80E-08 27 0.371147 0.01161 0.00212557 4.70E-08 28 0.949066 0.026977 0.00493877 4.70E-08 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 8: Genome-wide association study results for adulthood body size in the UK Biobank (Males only) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP ChromosomeBase position Closest gene Effect allele Other allele 7 rs62048402 16 53803223 FTO G A 8 rs374892365 2 633055 TMEM18 A T 9 rs7240682 18 57824038 MC4R C G 10 rs6265 11 27679916 BDNF C T 11 12 rs10938398 Confidential:4 45186139 GNPDA2 For ReviewG OnlyA 13 rs2526389 3 50192826 SEMA3F C T 14 rs7132908 12 50263148 FAIM2 G A 15 rs563738408 2 420443 FAM150B G A 16 rs3798519 6 50788778 TFAP2B A C 17 18 rs543874 1 177889480 SEC16B A G 19 rs61765650 1 72753112 NEGR1 A G 20 rs27741 16 28504181 CLN3 G A 21 rs28888492 7 76695502 UPK3B T C 22 23 rs7703782 5 87938557 MEF2C T A 24 rs1529897 2 25086827 ADCY3 T G 25 rs2678207 1 201825277 IPO9 C T 26 rs34517439 1 78450517 DNAJB4 C A 27 rs13107325 4 103188709 SLC39A8 C T 28 29 rs12919683 16 29943367 KCTD13 T C 30 rs10153031 15 67987293 MAP2K5 T G 31 rs3810291 19 47569003 ZC3H4 G A 32 rs7424120 2 59313974 FANCL C T 33 rs12798028 11 47604639 NDUFS3 C T 34 35 rs10132280 14 25928179 STXBP6 C A 36 rs1320903 3 131758077 CPNE4 G A 37 rs10423928 19 46182304 GIPR T A 38 rs17024258 1 110147321 GNAT2 C T 39 rs55742087 3 185830488 DGKG C T 40 41 rs62477735 7 75137097 POM121C A G 42 rs1652376 18 21109466 NPC1 G T 43 rs9317002 13 59175727 PCDH17 C A 44 rs1412239 9 28425515 LINGO2 C G 45 rs9901404 17 21213782 MAP2K3 A G 46 47 rs8008910 14 79944099 NRXN3 G A 48 rs12923231 16 69572892 NFAT5 C T 49 rs4477562 13 54104968 OLFM4 C T 50 rs12140153 1 62579891 INADL G T 51 rs4840941 8 8216986 SGK223 A G 52 53 rs181106785 18 58091681 MC4R T C 54 rs11780420 8 11446421 BLK G A 55 rs2143975 14 33297398 AKAP6 C G 56 rs13405033 2 113994595 PAX8 C T 57 rs1296328 4 137083193 PCDH18 A C 58 59 rs6054427 20 6635266 BMP2 G A 60 rs13066686 3 94075026 NSUN3 C A rs9320823 6 98429337 MMS22L T C

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1 2 rs1861410 2 58933591 FANCL C T 3 rs375636453 1 46324567 MAST2 T A 4 rs7940691 11 65640906 EFEMP2 C T 5 rs4898556 14 47299082 MDGA2 A C 6 7 rs9788550 14 29681138 PRKD1 G C 8 rs1887197 14 94187832 PRIMA1 C T 9 rs935166 2 26949366 KCNK3 G A 10 rs4755726 11 43642130 HSD17B12 T G 11 rs1451077 2 147901207 ACVR2A G A 12 Confidential: For Review Only 13 rs72674843 8 95533000 KIAA1429 T C 14 rs12149660 16 70309237 AARS G A 15 rs894000 3 183536063 MAP6D1 T C 16 rs2307111 5 75003678 POC5 T C 17 rs2918217 3 115546380 LSAMP C T 18 19 rs9277992 6 33312455 DAXX G A 20 rs11150745 17 78757626 RPTOR A G 21 rs9522279 13 112221296 RP11-65D24.2 C T 22 rs9469899 6 34793124 UHRF1BP1 G A 23 rs10883026 10 99793865 CRTAC1 C T 24 25 rs3923783 17 1843189 RTN4RL1 C A 26 rs73875019 3 131521276 CPNE4 T A 27 rs55782528 3 85893825 CADM2 C A 28 rs8192675 3 170724883 SLC2A2 T C 29 rs9329197 8 9259568 TNKS A T 30 31 rs3762444 1 2427712 PLCH2 C T 32 rs6970803 7 113005734 TSRM G T 33 rs6096886 20 50951298 ZFP64 A G 34 rs2181375 1 96940119 PTBP2 A G 35 rs217669 14 62360075 SYT16 T C 36 37 rs3750310 8 10283426 MSRA G A 38 rs2336558 3 52886240 TMEM110 C T 39 rs9471333 6 40362023 LRFN2 C T 40 rs6962280 7 44788657 ZMIZ2 A G 41 rs7308188 12 103701537 C12orf42 T C 42 43 rs147730268 12 123024476 KNTC1 G T 44 rs800526 8 116845729 TRPS1 A C 45 rs6069625 20 54747469 MC3R A G 46 rs7619139 3 25110415 RARB T A 47 rs62457529 7 32349219 PDE1C A G 48 49 rs117597828 10 102416055 PAX2 C T 50 rs62261477 3 48779421 IP6K2 G C 51 rs11631651 15 73646487 HCN4 A C 52 rs2260051 6 31591918 PRRC2A A T 53 rs1990573 16 9713688 RP11-297M9.1A G 54 55 rs11208779 1 66417145 PDE4B G C 56 rs3552 2 69698158 AAK1 G A 57 rs190043078 4 25377811 ANAPC4 A C 58 rs58243949 18 52509833 RAB27B C T 59 rs2591496 5 170516965 RANBP17 G A 60 rs35732620 8 73445881 KCNB2 G T

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1 2 rs1222216 11 30346052 ARL14EP C T 3 rs2125232 1 243759210 AKT3 C T 4 rs1568488 3 153657951 ARHGEF26 G C 5 rs9861443 3 88196211 CGGBP1 A C 6 7 rs57488047 15 79403002 RASGRF1 T C 8 rs9478671 6 155987825 NOX3 A G 9 rs17421586 22 40591312 TNRC6B T A 10 rs1888206 9 16735406 BNC2 A C 11 rs1459843 5 95867223 CAST C A 12 Confidential: For Review Only 13 rs8112818 19 18812785 CRTC1 A G 14 rs185575325 10 104665997 AS3MT C G 15 rs9977825 21 46494995 ADARB1 T C 16 rs2537860 4 55484718 KIT A C 17 rs4027773 10 16751164 RSU1 G T 18 19 rs11079849 17 47090785 IGF2BP1 C T 20 rs1284373 1 33355923 HPCA C T 21 rs1167311 1 49996959 AGBL4 G A 22 rs11619722 13 27998600 GTF3A T C 23 rs8054079 16 19975407 GPR139 C T 24 25 rs74621225 6 97804399 MMS22L A G 26 rs72867447 11 13301875 ARNTL C G 27 rs111946117 1 1590291 CDK11B C G 28 rs7983454 13 111850539 ARHGEF7 T C 29 rs12941009 17 34961051 MRM1 C T 30 31 rs17064653 3 61205741 FHIT T A 32 rs76895963 12 4384844 CCND2 T G 33 rs34052145 1 38824262 POU3F1 A G 34 rs566862115 2 198894544 PLCL1 T C 35 rs61789562 3 135926784 MSL2 T C 36 37 rs11708540 3 70593081 FOXP1 G A 38 rs8008772 14 88321884 GALC A T 39 rs12666574 7 26526960 KIAA0087 G A 40 rs7827210 8 30871656 PURG G A 41 rs7581907 2 205385454 PARD3B A G 42 43 rs12538826 7 99030228 PTCD1 T C 44 rs17145600 7 73994733 GTF2IRD1 C T 45 rs61954177 13 40787036 AL133318.1 G C 46 rs10236214 7 150668070 KCNH2 C T 47 rs72652703 8 67209548 CRH T C 48 49 rs10935143 3 134665159 EPHB1 G A 50 rs28881778 13 33177568 PDS5B T C 51 rs7232171 18 31251221 ASXL3 G T 52 rs1812736 8 76299138 HNF4G G A 53 rs61813324 1 156049877 MEX3A C T 54 55 rs4759228 12 56508409 PA2G4 G C 56 rs2238435 16 4014282 ADCY9 C G 57 rs6436661 2 228056670 COL4A3 C T 58 rs34714518 6 163080778 PARK2 G A 59 rs10828247 10 21822856 MLLT10 A G 60 rs4962671 10 126305434 LHPP T C

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1 2 rs6753397 2 105466651 POU3F3 C T 3 rs10898317 11 84613479 DLG2 C T 4 rs396354 2 86850022 CHMP3 T C 5 rs9379829 6 26172219 HIST1H2BD C T 6 7 rs10810413 9 15632205 CCDC171 G A 8 rs11616073 12 54644572 CBX5 T G 9 rs984225 1 119504284 TBX15 G A 10 rs13128760 4 18345588 LCORL C G 11 rs6490030 12 116106755 MED13L C A 12 Confidential: For Review Only 13 rs10131761 14 40752651 FBXO33 T A 14 rs10824218 10 76421216 ADK A T 15 rs55726687 12 991306 WNK1 G A 16 rs61992671 14 101531854 AL117190.3 A G 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 8: Genome-wide association study results for2 adulthood body size in the UK Biobank (Males only) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP3 on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.593948 -0.0473273 0.00195177 6.90E-130 8 0.172138 -0.0365162 0.002547 1.30E-46 9 0.771919 -0.0310971 0.00229614 8.70E-42 10 0.810786 0.0284965 0.00245086 3.00E-31 11 12 0.564934Confidential:-0.0214252 0.00193954 For Review2.30E-28 Only 13 0.573443 -0.019018 0.00193832 1.00E-22 14 0.61534 -0.0190074 0.0019712 5.30E-22 15 0.966147 0.0522231 0.00545791 1.10E-21 16 0.820254 -0.0235986 0.00250046 3.80E-21 17 18 0.794414 -0.0219623 0.00236863 1.80E-20 19 0.809614 0.0218588 0.00243508 2.80E-19 20 0.583875 -0.0172336 0.00194509 8.00E-19 21 0.80827 -0.0215871 0.0025284 1.40E-17 22 23 0.868286 -0.0235032 0.00281779 7.40E-17 24 0.568633 -0.0160487 0.00193238 1.00E-16 25 0.663696 -0.0167706 0.00202568 1.20E-16 26 0.878815 -0.0242191 0.00296972 3.50E-16 27 0.924027 -0.0294167 0.00362346 4.70E-16 28 29 0.450165 -0.0155587 0.00192655 6.70E-16 30 0.398337 -0.0156337 0.00196767 1.90E-15 31 0.325746 -0.0159616 0.00204687 6.30E-15 32 0.398625 0.0152821 0.00196182 6.70E-15 33 0.591888 -0.0150728 0.00194615 9.60E-15 34 35 0.698004 0.0162593 0.00210069 9.90E-15 36 0.680836 -0.0158846 0.00205867 1.20E-14 37 0.80618 0.0187059 0.00242362 1.20E-14 38 0.974128 -0.0465101 0.00604591 1.40E-14 39 0.814697 0.0189962 0.00247061 1.50E-14 40 41 0.577459 0.014902 0.00194956 2.10E-14 42 0.538172 0.0146717 0.00192678 2.60E-14 43 0.486133 -0.014688 0.00193306 3.00E-14 44 0.678123 -0.01546 0.00204677 4.20E-14 45 0.472684 0.0155025 0.00208654 1.10E-13 46 47 0.777645 -0.0169668 0.00231444 2.30E-13 48 0.590018 0.0141876 0.00195449 3.90E-13 49 0.870863 -0.0206719 0.00288645 8.00E-13 50 0.905264 0.0238165 0.0033476 1.10E-12 51 0.469723 -0.0136679 0.00194489 2.10E-12 52 53 0.974609 0.0445804 0.00635281 2.30E-12 54 0.41539 0.013585 0.00195456 3.60E-12 55 0.466424 0.0133881 0.00193561 4.60E-12 56 0.845882 -0.0183218 0.00265897 5.60E-12 57 0.440379 0.013313 0.0019411 7.00E-12 58 59 0.378433 -0.0135725 0.00198908 8.90E-12 60 0.594046 0.0132647 0.00195767 1.20E-11 0.396931 -0.0132728 0.00196194 1.30E-11

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1 2 0.445596 0.0130573 0.00193511 1.50E-11 3 0.958748 0.0326246 0.0048546 1.80E-11 4 0.36113 0.0134052 0.00199441 1.80E-11 5 0.491805 0.0128947 0.00192001 1.90E-11 6 7 0.753278 0.0149898 0.00223434 2.00E-11 8 0.346668 -0.0136529 0.00204297 2.30E-11 9 0.492924 0.0127958 0.00191695 2.50E-11 10 0.310196 0.0138489 0.00207554 2.50E-11 11 0.414407 0.012968 0.00194606 2.70E-11 12 Confidential: For Review Only 13 0.760918 0.0149869 0.00225177 2.80E-11 14 0.885019 0.0200898 0.00302327 3.00E-11 15 0.372132 0.0131566 0.00198821 3.70E-11 16 0.604888 0.0129985 0.00196472 3.70E-11 17 0.8593 -0.0182235 0.00278109 5.70E-11 18 19 0.810303 -0.0160305 0.00245673 6.80E-11 20 0.68261 0.0134599 0.00206252 6.80E-11 21 0.576583 -0.012687 0.00194739 7.30E-11 22 0.640453 -0.0129955 0.00200003 8.20E-11 23 0.479175 0.0125097 0.00193565 1.00E-10 24 25 0.815451 0.0159843 0.00247377 1.00E-10 26 0.883333 0.0194613 0.00301306 1.10E-10 27 0.646282 0.0129023 0.00200476 1.20E-10 28 0.711835 -0.0135129 0.00211474 1.70E-10 29 0.380418 0.0128475 0.00201335 1.80E-10 30 31 0.545532 0.0123275 0.00193979 2.10E-10 32 0.629759 -0.0128215 0.00202267 2.30E-10 33 0.809688 0.0155007 0.00244715 2.40E-10 34 0.403399 -0.0123305 0.00195121 2.60E-10 35 0.728012 -0.0135655 0.00215989 3.40E-10 36 37 0.487655 0.0120546 0.00192271 3.60E-10 38 0.383956 0.0122968 0.00196423 3.80E-10 39 0.447184 0.0120522 0.00192522 3.80E-10 40 0.442377 -0.0121406 0.00193843 3.80E-10 41 0.745359 0.0136658 0.0022008 5.30E-10 42 43 0.913273 0.0215819 0.00348793 6.10E-10 44 0.223183 -0.014195 0.00230294 7.10E-10 45 0.726408 0.0134094 0.00217583 7.10E-10 46 0.410674 -0.0119605 0.00195334 9.20E-10 47 0.891175 -0.0188372 0.00307832 9.40E-10 48 49 0.782342 -0.0142523 0.00233372 1.00E-09 50 0.917916 -0.021311 0.00350018 1.10E-09 51 0.927041 0.0224761 0.00370504 1.30E-09 52 0.439011 -0.0116737 0.00192902 1.40E-09 53 0.306499 -0.0125459 0.00208178 1.70E-09 54 55 0.471079 -0.01154 0.0019202 1.90E-09 56 0.458141 -0.0115186 0.00192171 2.00E-09 57 0.769093 0.0139933 0.00233543 2.10E-09 58 0.767187 -0.0136188 0.0022792 2.30E-09 59 0.270157 -0.0128877 0.00216054 2.40E-09 60 0.425255 0.0115809 0.0019452 2.60E-09

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1 2 0.773331 0.0136223 0.00228865 2.60E-09 3 0.318088 0.012243 0.00205849 2.70E-09 4 0.405308 -0.01169 0.00196599 2.70E-09 5 0.284775 -0.0127066 0.00213714 2.80E-09 6 7 0.532046 0.0115127 0.001941 3.00E-09 8 0.789465 -0.0139941 0.00236188 3.10E-09 9 0.660063 0.0119847 0.00202795 3.40E-09 10 0.720778 -0.0131312 0.00222501 3.60E-09 11 0.392366 0.0115397 0.00196345 4.20E-09 12 Confidential: For Review Only 13 0.600634 0.0115319 0.00196753 4.60E-09 14 0.925516 -0.0213876 0.00367335 5.80E-09 15 0.360821 0.0116791 0.00200559 5.80E-09 16 0.436875 0.0113708 0.00195512 6.00E-09 17 0.359877 -0.0116656 0.00200734 6.20E-09 18 19 0.672005 0.0118925 0.00204809 6.40E-09 20 0.801176 0.0138811 0.00239569 6.90E-09 21 0.319262 0.0120025 0.00207277 7.00E-09 22 0.699176 0.0121375 0.00209665 7.10E-09 23 0.859577 0.0160916 0.00279735 8.80E-09 24 25 0.865845 0.0162566 0.00282678 8.90E-09 26 0.428299 -0.0111135 0.00193613 9.50E-09 27 0.736996 0.0125361 0.00219246 1.10E-08 28 0.476725 0.010963 0.00192203 1.20E-08 29 0.597899 0.0112482 0.00197508 1.20E-08 30 31 0.780356 0.0131733 0.00231692 1.30E-08 32 0.979262 -0.0421932 0.00741682 1.30E-08 33 0.647338 -0.0114425 0.00201656 1.40E-08 34 0.950603 0.0288965 0.00510489 1.50E-08 35 0.882131 0.0167865 0.00296621 1.50E-08 36 37 0.842895 -0.0149659 0.00264764 1.60E-08 38 0.749831 -0.0125701 0.00222668 1.60E-08 39 0.326829 -0.011583 0.00205239 1.70E-08 40 0.603592 -0.0110992 0.00196644 1.70E-08 41 0.127168 0.0162375 0.00289543 2.00E-08 42 43 0.884989 0.0168625 0.00300495 2.00E-08 44 0.949247 -0.0245046 0.00436953 2.00E-08 45 0.673076 -0.0115225 0.00205217 2.00E-08 46 0.357514 -0.011281 0.00201192 2.10E-08 47 0.745013 0.0123802 0.00221076 2.10E-08 48 49 0.551479 0.0107967 0.00192903 2.20E-08 50 0.633251 0.0112006 0.00200076 2.20E-08 51 0.417747 -0.0108821 0.00194602 2.20E-08 52 0.173741 -0.0142297 0.00254572 2.30E-08 53 0.864038 -0.0158125 0.00283289 2.40E-08 54 55 0.703395 0.0117325 0.00210613 2.50E-08 56 0.38597 -0.0110063 0.00197462 2.50E-08 57 0.113215 -0.0184186 0.00330969 2.60E-08 58 0.876832 0.0162691 0.00292213 2.60E-08 59 0.656904 -0.0112382 0.00202227 2.70E-08 60 0.531657 0.0107379 0.00193174 2.70E-08

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1 2 0.725178 -0.0119792 0.0021619 3.00E-08 3 0.487356 0.0106527 0.00192212 3.00E-08 4 0.284513 0.0117717 0.00212711 3.10E-08 5 0.7823 0.0128604 0.00232369 3.10E-08 6 7 0.625617 0.0114085 0.00206158 3.10E-08 8 0.590424 0.0107847 0.00194878 3.10E-08 9 0.389371 0.0108351 0.00196328 3.40E-08 10 0.707041 -0.0116187 0.00211107 3.70E-08 11 0.62602 -0.010953 0.00199126 3.80E-08 12 Confidential: For Review Only 13 0.811592 0.0135109 0.00246038 4.00E-08 14 0.563347 0.0106455 0.00194882 4.70E-08 15 0.791592 -0.0128872 0.00235856 4.70E-08 16 0.50787 0.0109576 0.00200831 4.90E-08 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 9: Genome-wide association study results for early life body size in the UK Biobank (with additional adjustment for month of birth) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs1421085 16 53800954 FTO T C 8 rs543874 1 177889480 SEC16B A G 9 10 rs10182458 2 25150641 ADCY3 A G 11 rs62106258 2 417167 FAM150B T C 12 rs12992672 Confidential:2 632592 ForTMEM18 ReviewG OnlyA 13 rs7132908 12 50263148 FAIM2 G A 14 15 rs663129 18 57838401 MC4R G A 16 rs12042908 1 74997762 FPGT-TNNI3K A G 17 rs12042908 1 74997762 TNNI3K A G 18 19 rs12641981 4 45179883 GNPDA2 C T 20 rs55880046 16 19941557 GPRC5B T G 21 rs115319174 2 207066474 GPR1 G C 22 rs3798519 6 50788778 TFAP2B A C 23 24 rs11209943 1 72750500 NEGR1 A G 25 rs8030456 15 68076856 MAP2K5 C T 26 rs35918296 8 76862208 HNF4G C T 27 28 rs2238435 16 4014282 ADCY9 C G 29 rs7550711 1 110082886 GPR61 C T 30 rs4744246 9 96254464 FAM120A A G 31 rs34260097 6 100727703 SIM1 T G 32 33 rs12798028 11 47604639 NDUFS3 C T 34 rs56133711 11 27723334 BDNF G A 35 rs12110721 6 55190480 GFRAL G A 36 37 rs3810291 19 47569003 ZC3H4 G A 38 rs12429545 13 54102206 OLFM4 G A 39 rs1933437 13 28624294 FLT3 G A 40 rs113728099 18 58157767 MC4R G A 41 42 rs7377083 4 102708997 BANK1 C A 43 rs62037365 16 28868962 SH2B1 C G 44 rs7719067 5 153538241 MFAP3 A G 45 46 rs9265968 6 31315663 HLA-B A T 47 rs7239114 18 45921214 ZBTB7C G A 48 rs1775255 6 51243035 PKHD1 G T 49 rs75001243 7 93216002 GNGT1 C T 50 51 rs9260164 6 29911684 HLA-A C T 52 rs61978655 14 30491807 PRKD1 G A 53 rs16996644 20 15813475 MACROD2 C G 54 55 rs7084503 10 2666859 PFKP T C 56 rs4688359 3 61198880 FHIT C T 57 rs9291816 5 63932508 RGS7BP C T 58 rs12140153 1 62579891 INADL G T 59 60 rs7355953 3 85792137 CADM2 T C rs7958241 12 49509262 LMBR1L A G

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1 2 rs2767486 1 65991203 LEPR A G 3 rs35162296 6 26318262 HIST1H4H C T 4 rs41310284 10 102447647 PAX2 C A 5 6 rs1384660 2 142299735 LRP1B G A 7 rs3131336 6 28831611 TRIM27 C T 8 rs34196306 6 27425644 ZNF184 G C 9 10 rs3129942 6 32338283 C6orf10 G T 11 rs2303384 11 65640204 EFEMP2 C T 12 rs9603697 Confidential:13 40783323 ForAL133318.1 ReviewC OnlyT 13 rs200744777 20 6609610 BMP2 T G 14 15 rs13047416 21 40309436 ETS2 C G 16 rs6001872 22 40703245 TNRC6B A G 17 rs13254613 8 64804804 YTHDF3 A C 18 19 rs2594994 3 11339960 ATG7 T A 20 rs796915 6 154304628 OPRM1 C G 21 rs55726687 12 991306 WNK1 G A 22 rs1333010 13 66205228 PCDH9 G A 23 24 rs4432271 16 20245283 GP2 C T 25 rs78444298 1 184672098 EDEM3 G A 26 rs9538141 13 59178258 PCDH17 G A 27 28 rs117903946 16 67449639 ZDHHC1 G A 29 rs1576655 13 79587841 RBM26 A C 30 rs11215403 11 115058585 CADM1 G A 31 rs59714050 3 141267294 RASA2 T A 32 33 rs72819571 17 2170501 SMG6 G T 34 rs7656673 4 30840331 PCDH7 A G 35 rs11150745 17 78757626 RPTOR A G 36 37 rs2207894 20 54387343 CBLN4 C T 38 rs11642090 16 81730582 CMIP T C 39 rs788858 4 82138300 PRKG2 A G 40 rs72755233 15 100692953 ADAMTS17 G A 41 42 rs818898 9 6970806 KDM4C A G 43 rs2409743 8 11070360 XKR6 C G 44 rs12713889 2 77225361 LRRTM4 T C 45 46 rs2722406 7 24306762 NPY C T 47 rs2735556 3 88105360 CGGBP1 T C 48 rs13256357 8 9979535 MSRA C T 49 rs10796828 11 69490346 ORAOV1 T G 50 51 rs2187642 12 11855624 ETV6 A C 52 rs12606230 18 52492252 RAB27B T C 53 rs6449532 5 60715446 ZSWIM6 C T 54 55 rs1013737 18 937050 ADCYAP1 G C 56 rs10896348 11 68357368 PPP6R3 T C 57 rs17399739 10 87490850 GRID1 A G 58 rs17637472 17 47461433 RP11-81K2.1 G A 59 60 rs71231793 7 76682610 UPK3B T C rs1199333 3 138091701 MRAS G T

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1 2 rs2034963 3 48170802 CDC25A G C 3 rs39862 5 66185151 MAST4 T C 4 rs1865719 14 79923667 NRXN3 A G 5 6 rs11777719 8 8581038 CLDN23 A G 7 rs1342831 6 54096151 MLIP T C 8 rs7989098 13 27925496 GTF3A T C 9 10 rs7989098 13 27925496 GTF3A T C 11 rs11525873 7 138817193 TTC26 T C 12 rs117911387Confidential:9 130446836 ForSTXBP1 ReviewG OnlyA 13 rs2229330 1 6649228 ZBTB48 T G 14 15 rs9438393 1 205782718 SLC41A1 A G 16 rs200801362 6 31555480 LST1 T C 17 rs7161424 14 33309274 AKAP6 G A 18 19 rs116399833 19 18502374 LRRC25 C A 20 rs754635 3 42305131 CCK C G 21 rs1935354 9 27822531 LINGO2 T C 22 rs2275241 9 129370576 LMX1B G A 23 24 rs12214497 6 10015908 OFCC1 G T 25 rs630602 1 54728864 SSBP3 G C 26 rs7306710 12 66376091 HMGA2 T C 27 28 rs78607331 12 57648644 R3HDM2 C T 29 rs78607331 12 57648644 RP11-123K3.4 C T 30 rs4889630 16 30877544 BCL7C T C 31 rs7606059 2 188152749 CALCRL T C 32 33 rs77960 5 103964585 NUDT12 G A 34 rs7305424 12 118399491 KSR2 A T 35 rs61937656 12 39483502 CPNE8 G A 36 37 rs73422097 6 41727740 PGC A G 38 rs957512 9 120405705 TLR4 T C 39 rs1452991 6 141473363 NMBR G A 40 rs7619139 3 25110415 RARB T A 41 42 rs10790809 11 126372550 KIRREL3 A G 43 rs355748 3 153964496 ARHGEF26 G T 44 rs7012648 8 28091482 ELP3 G A 45 46 rs947088 20 17171373 PCSK2 G T 47 rs72675820 4 130746149 C4orf33 A C 48 rs836179 12 50503082 GPD1 A G 49 rs7625768 3 131774642 CPNE4 G A 50 51 rs3817428 15 89415247 ACAN C G 52 rs11205303 1 149906413 MTMR11 T C 53 rs62425398 6 166416028 PDE10A C A 54 55 rs601338 19 49206674 FUT2 G A 56 rs112898427 2 67561335 ETAA1 C T 57 rs146910503 2 25446473 DNMT3A G A 58 rs6979832 7 127856276 LEP A G 59 60 rs7808296 7 103127620 RELN C T rs661878 11 29188691 METTL15 A G

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1 2 rs1800437 19 46181392 GIPR G C 3 rs7759938 6 105378954 LIN28B C T 4 rs7237444 18 39468982 PIK3C3 G A 5 6 rs824207 15 24007729 NDN A G 7 rs7162542 15 84514290 ADAMTSL3 C G 8 rs4074404 1 187683956 PLA2G4A T A 9 10 rs2970356 15 90623540 ZNF710 C G 11 rs1422067 5 77424836 AP3B1 C T 12 rs12045879 Confidential:1 15817090 ForCELA2B ReviewC OnlyT 13 rs9299 17 46669430 HOXB3 C T 14 15 rs9299 17 46669430 HOXB5 C T 16 rs1808579 18 21104888 C18orf8 C T 17 rs1808579 18 21104888 NPC1 C T 18 19 rs9366803 6 32621132 HLA-DQB1 T C 20 rs10095724 8 53739232 RB1CC1 G A 21 rs7020564 9 109670016 ZNF462 A T 22 rs28629903 12 122497001 BCL7A T C 23 24 rs7536458 1 118864602 SPAG17 T G 25 rs8048855 16 24830839 TNRC6A G T 26 rs4572029 10 70889053 VPS26A A G 27 28 rs34517439 1 78450517 DNAJB4 C A 29 rs34517439 1 78450517 GIPC2 C A 30 rs62175963 2 161339964 RBMS1 T C 31 rs4958568 5 152016093 NMUR2 G A 32 33 rs2246623 17 74084449 EXOC7 C T 34 rs8096658 18 77156537 NFATC1 C G 35 rs2141004 2 6194359 DKFZP761K2322A C 36 37 rs918472 5 170738836 TLX3 G A 38 rs35588936 1 155950963 ARHGEF2 C T 39 rs10133279 14 82702712 SEL1L C T 40 rs77976727 8 4300554 CSMD1 C T 41 42 rs9922288 16 24550930 RBBP6 A G 43 rs2629881 3 59778271 FHIT C T 44 rs78907487 22 22151939 MAPK1 A C 45 46 rs10503246 8 4130363 CSMD1 A G 47 rs4985555 16 70690166 IL34 A G 48 rs35926495 3 50255663 GNAI2 C T 49 rs262338 7 103417134 RELN G T 50 51 rs7753558 6 117523471 VGLL2 C A 52 rs435775 6 97237609 GPR63 A G 53 rs7951870 11 46373311 DGKZ T C 54 55 rs35189091 4 137147696 PCDH18 A G 56 rs6783281 3 84791851 CADM2 A G 57 rs1552759 12 99640557 ANKS1B T C 58 rs2356864 1 50839740 DMRTA2 G A 59 60 rs7522014 1 66551759 PDE4B A G rs3810304 19 30861683 ZNF536 A G

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1 2 rs34811474 4 25408838 ANAPC4 G A 3 rs212517 1 21577159 ECE1 T A 4 rs62134189 2 45046339 CAMKMT A G 5 6 rs2115885 5 87598818 TMEM161B G A 7 rs62621197 19 8670147 ADAMTS10 C T 8 rs2307111 5 75003678 POC5 T C 9 10 rs3936511 5 55860781 AC022431.2 A G 11 rs10234366 7 46743746 AC011294.3 G A 12 rs4808961 Confidential:19 19577215 ForGATAD2A ReviewC OnlyG 13 rs117455294 20 57427951 GNAS C A 14 15 rs4267058 11 28645584 METTL15 T C 16 rs3013431 1 113242488 MOV10 C T 17 rs2867116 2 682363 TMEM18 C A 18 19 rs75387636 10 120278394 PRLHR G A 20 rs2281148 20 36433288 CTNNBL1 T C 21 rs1852006 7 77829768 MAGI2 G A 22 rs10962279 9 16103030 CCDC171 T C 23 24 rs12817542 12 103736499 C12orf42 C T 25 rs2902142 2 58849805 FANCL C T 26 rs10860295 12 98542699 RP11-181C3.1 T C 27 28 rs6940215 6 34706358 SNRPC G A 29 rs10498713 6 22729300 HDGFL1 G T 30 rs7814267 8 5545084 CSMD1 A G 31 rs146980124 17 44627649 ARL17A A C 32 33 rs146980124 17 44627649 LRRC37A2 A C 34 rs8117463 20 17231063 PCSK2 G A 35 rs10953577 7 108263540 DNAJB9 T C 36 37 rs67603370 17 7524504 SHBG G A 38 rs12748436 1 177761109 SEC16B C G 39 rs11891707 2 207120604 ZDBF2 T C 40 rs4723263 7 33194826 BBS9 G C 41 42 rs7123283 11 122809055 C11orf63 C T 43 rs7145052 14 92461192 TRIP11 C T 44 rs10842356 12 24621348 BCAT1 A T 45 46 rs9652090 13 27983367 GTF3A G T 47 rs62032001 16 49065630 CBLN1 A C 48 rs12436513 14 103269755 TRAF3 C A 49 rs7633995 3 180369750 CCDC39 A G 50 51 rs3181269 11 33755956 CD59 C T 52 rs10116891 9 122651993 RP11-295D22.1G A 53 rs884152 8 25770557 EBF2 G T 54 55 rs3118252 9 25115154 TUSC1 G C 56 rs6931604 6 98578215 POU3F2 C T 57 rs636402 2 219466859 RQCD1 T C 58 rs9594686 13 42723197 DGKH C T 59 60 rs9611560 22 41750622 ZC3H7B T C rs4739558 8 38337264 FGFR1 A G

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1 2 rs686431 6 35974217 SLC26A8 C T 3 rs7817581 8 143136114 TSNARE1 G A 4 rs1666132 3 77649190 ROBO2 C T 5 6 rs9370527 6 56245812 COL21A1 G A 7 rs7354849 1 232765308 SIPA1L2 A G 8 rs61936936 12 116391685 MED13L A T 9 10 rs7672 16 68294800 PLA2G15 C G 11 rs7503580 17 79087036 BAIAP2 C T 12 rs2242258 Confidential:10 75607168 ForCAMK2G ReviewT OnlyC 13 rs7711823 5 158489315 EBF1 A G 14 15 rs11256627 10 10535954 CELF2 G A 16 rs11165687 1 97099767 PTBP2 C T 17 rs7565437 2 65646966 SPRED2 T C 18 19 rs1696058 12 90767159 CCER1 T C 20 rs115359679 7 755987 PRKAR1B C A 21 rs12941038 17 66509143 PRKAR1A C T 22 rs10937241 3 185822774 ETV5 A G 23 24 rs12308065 12 120624085 GCN1L1 A G 25 rs4545941 19 16534207 EPS15L1 T C 26 rs201666051 9 20920868 FOCAD C T 27 28 rs1177279 2 61295122 KIAA1841 A G 29 rs7439324 4 44501351 KCTD8 C T 30 rs4783789 16 51446707 SALL1 T C 31 rs1476698 2 242296449 FARP2 A G 32 33 rs6974282 7 100098295 NYAP1 C T 34 rs71483681 11 131469205 NTM T C 35 rs116293915 12 42705738 PPHLN1 C A 36 37 rs2755253 1 67470843 SLC35D1 C T 38 rs115903965 3 66009529 MAGI1 G A 39 rs34722008 4 38659594 AC021860.1 G A 40 rs10519136 15 47933163 SEMA6D C T 41 42 rs2539692 2 59841988 BCL11A T A 43 rs1619120 9 87302196 NTRK2 A G 44 rs10887571 10 88030441 GRID1 C T 45 46 rs2958542 11 62181882 SCGB1A1 C T 47 rs6577497 1 8605667 RERE A T 48 rs2939931 10 121636406 MCMBP T C 49 rs12132598 1 115235785 AMPD1 A G 50 51 rs7840305 8 57168101 CHCHD7 A G 52 rs3815156 17 29685150 NF1 A G 53 rs8130408 21 39237138 KCNJ6 A C 54 55 rs1061072 10 126684796 CTBP2 G A 56 rs2268762 3 38516075 ACVR2B A G 57 rs538579 3 62711674 CADPS G C 58 rs7159126 14 93783176 BTBD7 T C 59 60 rs1402989 3 27056851 NEK10 C T rs7217460 17 65393344 PITPNC1 G A

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1 2 rs6719507 2 29733801 ALK G A 3 rs10841379 12 19992303 AEBP2 A G 4 rs3862342 11 49357043 FOLH1 C T 5 6 rs594585 16 65939803 CDH5 T G 7 rs73085586 20 22430241 FOXA2 G A 8 rs11925138 3 131626048 CPNE4 G A 9 10 rs11727676 4 145659064 HHIP T C 11 rs16839832 1 196349909 KCNT2 G T 12 rs76187039 Confidential:6 43233990 ForTTBK1 ReviewG OnlyT 13 rs3791478 2 240064139 HDAC4 T C 14 15 rs10791902 11 67093360 SSH3 C T 16 rs78420139 14 101201687 DLK1 G A 17 rs4677156 3 72417857 RYBP A T 18 19 rs10823504 10 72034062 NPFFR1 G A 20 rs1000471 15 89986583 RHCG C T 21 rs2175171 1 7028842 CAMTA1 G C 22 rs10503555 8 15763818 TUSC3 A G 23 24 rs9610387 22 36476762 RBFOX2 G A 25 rs62048187 15 38117049 TMCO5A G C 26 rs1357798 3 83780583 CADM2 C T 27 28 rs10111937 8 54160092 OPRK1 C T 29 rs12601380 17 34904985 GGNBP2 A C 30 rs68015088 18 51484010 MBD2 G A 31 rs3774604 3 53824136 CACNA1D C T 32 33 rs67679818 7 110672704 IMMP2L C T 34 rs772175 2 96944553 SNRNP200 G A 35 rs2349179 7 8404389 NXPH1 T A 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 9: Genome-wide association study results for 2early life body size in the UK Biobank (with additional adjustment for month of birth) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP3 on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequency Beta Standard Error P 7 0.596552 -0.0473859 0.00142731 1.10E-241 8 0.794752 -0.0470912 0.00173201 8.80E-163 9 10 0.513877 -0.035916 0.00139959 3.10E-145 11 0.951459 0.080258 0.00325353 2.40E-134 12 Confidential:0.171864 -0.0433211 0.00185218 For Review5.50E-121 Only 13 0.615537 -0.0312612 0.00144002 1.70E-104 14 15 0.766595 -0.0332603 0.00165548 8.80E-90 16 0.437703 0.0274639 0.00141114 2.30E-84 17 0.437703 0.0274639 0.00141114 2.30E-84 18 19 0.565002 -0.0221856 0.00141516 2.20E-55 20 0.857664 0.0298592 0.00200506 3.70E-50 21 0.942407 -0.0423001 0.00303582 4.00E-44 22 0.820086 -0.0249912 0.00182368 9.70E-43 23 24 0.396432 -0.0183324 0.00142764 9.70E-38 25 0.773633 0.0213234 0.00167055 2.60E-37 26 0.586164 0.0166279 0.00142396 1.70E-31 27 28 0.386247 -0.0164841 0.00144201 2.90E-30 29 0.973981 -0.0484762 0.00441208 4.40E-28 30 0.656346 -0.0157518 0.00147886 1.70E-26 31 0.776056 -0.0178199 0.00167851 2.50E-26 32 33 0.591453 -0.0145789 0.00142175 1.10E-24 34 0.7406 -0.016226 0.00159844 3.30E-24 35 0.825618 -0.0189304 0.00189373 1.60E-23 36 37 0.324953 -0.0147598 0.00149533 5.60E-23 38 0.870646 -0.0206274 0.00210597 1.20E-22 39 0.374865 0.0141194 0.00144563 1.60E-22 40 0.975264 0.0439079 0.00454359 4.30E-22 41 42 0.568979 -0.013716 0.00142534 6.40E-22 43 0.601978 -0.013698 0.00143014 9.90E-22 44 0.427582 0.0134965 0.00141391 1.40E-21 45 46 0.866272 -0.0201199 0.00210963 1.50E-21 47 0.458349 -0.0134876 0.00141723 1.80E-21 48 0.523411 -0.0133343 0.00140502 2.30E-21 49 0.640117 -0.0137392 0.00145963 4.80E-21 50 51 0.737668 -0.0151448 0.00161422 6.50E-21 52 0.961364 -0.033958 0.00364734 1.30E-20 53 0.873026 -0.0193484 0.00211031 4.80E-20 54 55 0.491843 0.0128811 0.0014078 5.70E-20 56 0.626072 0.0130228 0.00144862 2.50E-19 57 0.676351 0.0134228 0.00149771 3.20E-19 58 0.905761 0.0218143 0.00245448 6.20E-19 59 60 0.784962 -0.0151808 0.00170925 6.60E-19 0.656021 -0.0130763 0.00147559 7.90E-19

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1 2 0.797514 -0.0153791 0.00174285 1.10E-18 3 0.894147 -0.020031 0.00227175 1.20E-18 4 0.898985 0.0205882 0.00234105 1.40E-18 5 6 0.814942 0.0157939 0.00180243 1.90E-18 7 0.882895 -0.0190496 0.00217718 2.10E-18 8 0.893449 -0.019962 0.00228684 2.60E-18 9 10 0.742436 -0.0139298 0.00159838 2.90E-18 11 0.359636 0.0126783 0.00145724 3.30E-18 12 Confidential:0.673168 -0.0129432 0.00149578 For Review5.00E-18 Only 13 0.561375 -0.0121414 0.00142158 1.30E-17 14 15 0.622962 0.0123762 0.00145063 1.40E-17 16 0.65069 0.0125519 0.0014723 1.50E-17 17 0.654054 -0.0125636 0.00147493 1.60E-17 18 19 0.178094 0.0154935 0.00183004 2.50E-17 20 0.305175 -0.0128931 0.00152331 2.60E-17 21 0.79024 -0.0145374 0.00171837 2.70E-17 22 0.389639 0.0120542 0.00143818 5.20E-17 23 24 0.131408 -0.0174978 0.00210753 1.00E-16 25 0.980505 0.0420029 0.00509728 1.70E-16 26 0.486394 -0.0115923 0.00141182 2.20E-16 27 28 0.967498 -0.0322423 0.003949 3.20E-16 29 0.404079 -0.0118531 0.00145786 4.30E-16 30 0.757269 0.0132511 0.00163429 5.10E-16 31 0.933673 -0.0228199 0.00281485 5.20E-16 32 33 0.652316 0.0118772 0.0014708 6.70E-16 34 0.599358 -0.0115396 0.00142921 6.80E-16 35 0.68227 0.0121632 0.00150724 7.00E-16 36 37 0.808677 0.0143441 0.00178112 8.00E-16 38 0.626428 -0.0117252 0.00145879 9.20E-16 39 0.706844 0.0123153 0.00154337 1.50E-15 40 0.888558 -0.0176469 0.00222453 2.10E-15 41 42 0.31586 0.0120555 0.00152234 2.40E-15 43 0.503174 0.0110663 0.00140249 3.00E-15 44 0.670052 0.0116923 0.00148689 3.70E-15 45 46 0.715873 -0.0121843 0.00155476 4.60E-15 47 0.885665 0.0172019 0.00219664 4.80E-15 48 0.798517 -0.0136536 0.00175085 6.30E-15 49 0.365603 -0.0113349 0.00145631 7.10E-15 50 51 0.37581 -0.011155 0.00144452 1.10E-14 52 0.766455 -0.0127526 0.00165794 1.50E-14 53 0.63966 0.0110529 0.0014571 3.30E-14 54 55 0.506779 -0.0106427 0.00140313 3.30E-14 56 0.723747 0.0118588 0.00156399 3.40E-14 57 0.931102 -0.0209712 0.0027706 3.80E-14 58 0.601401 -0.010909 0.00144363 4.10E-14 59 60 0.841645 -0.0153981 0.00204201 4.70E-14 0.184152 0.0135345 0.00180297 6.10E-14

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1 2 0.35132 0.0110936 0.00147955 6.50E-14 3 0.717446 0.0116463 0.00155705 7.40E-14 4 0.367072 -0.0109002 0.00146053 8.40E-14 5 6 0.715936 -0.011653 0.00156172 8.50E-14 7 0.942918 -0.0224973 0.00301586 8.70E-14 8 0.258487 -0.0120968 0.00162621 1.00E-13 9 10 0.258487 -0.0120968 0.00162621 1.00E-13 11 0.902215 0.0174305 0.00236292 1.60E-13 12 Confidential:0.953645 -0.0245837 0.0033306For Review1.60E-13 Only 13 0.92759 -0.0197644 0.00269415 2.20E-13 14 15 0.585662 0.0103602 0.00142153 3.10E-13 16 0.839907 -0.0188503 0.00259503 3.80E-13 17 0.520764 -0.0102644 0.00141767 4.50E-13 18 19 0.77367 -0.0123406 0.00170532 4.60E-13 20 0.113398 -0.0159112 0.00220628 5.50E-13 21 0.51711 -0.0101328 0.00140539 5.60E-13 22 0.628088 -0.0104243 0.00144901 6.30E-13 23 24 0.654505 0.0105085 0.00147294 9.70E-13 25 0.393414 -0.0101746 0.00143972 1.60E-12 26 0.47969 0.00996155 0.00141048 1.60E-12 27 28 0.955251 -0.0238858 0.00338447 1.70E-12 29 0.955251 -0.0238858 0.00338447 1.70E-12 30 0.19996 0.0123248 0.00175011 1.90E-12 31 0.335053 -0.0104987 0.00149573 2.20E-12 32 33 0.671971 0.0104759 0.00149259 2.20E-12 34 0.657832 -0.0104024 0.00148311 2.30E-12 35 0.773702 0.0117312 0.00167808 2.70E-12 36 37 0.698774 -0.0106329 0.00152465 3.10E-12 38 0.669786 0.0103274 0.0014938 4.70E-12 39 0.627782 -0.0100544 0.00145809 5.40E-12 40 0.411293 -0.00980824 0.00142669 6.20E-12 41 42 0.44025 -0.00966457 0.00141001 7.20E-12 43 0.62244 -0.00992628 0.00144886 7.30E-12 44 0.414981 -0.00973898 0.00142575 8.40E-12 45 46 0.282112 -0.0106403 0.0015617 9.50E-12 47 0.357101 0.009938 0.00146064 1.00E-11 48 0.630603 0.00983503 0.00145102 1.20E-11 49 0.682031 -0.0101882 0.00150607 1.30E-11 50 51 0.735103 -0.0107532 0.00158826 1.30E-11 52 0.593282 0.00959504 0.00142525 1.70E-11 53 0.893663 -0.0153325 0.00228405 1.90E-11 54 55 0.49204 0.00937556 0.00139988 2.10E-11 56 0.299591 0.0103291 0.00154959 2.60E-11 57 0.978757 0.0334637 0.00502502 2.70E-11 58 0.503006 -0.00938812 0.00140943 2.70E-11 59 60 0.684557 -0.0100387 0.00150798 2.80E-11 0.866936 0.0137266 0.00206137 2.80E-11

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1 2 0.80578 0.0117602 0.00176856 2.90E-11 3 0.321912 -0.00994913 0.00149939 3.20E-11 4 0.327748 0.0100816 0.00152132 3.40E-11 5 6 0.465213 -0.00928998 0.00140394 3.70E-11 7 0.442849 0.00932825 0.00141064 3.80E-11 8 0.840611 -0.0126796 0.00192281 4.30E-11 9 10 0.679324 -0.0104353 0.00158448 4.50E-11 11 0.762745 0.0108312 0.00164516 4.60E-11 12 Confidential:0.686864 0.00988742 0.00150645 For Review5.30E-11 Only 13 0.343455 -0.00959927 0.00147345 7.30E-11 14 15 0.343455 -0.00959927 0.00147345 7.30E-11 16 0.517857 0.00913203 0.00140361 7.70E-11 17 0.517857 0.00913203 0.00140361 7.70E-11 18 19 0.683074 -0.010776 0.00167134 1.10E-10 20 0.637545 0.00938105 0.0014609 1.40E-10 21 0.702174 0.00997181 0.00155313 1.40E-10 22 0.435592 0.00907014 0.00141557 1.50E-10 23 24 0.737635 -0.0101349 0.0015886 1.80E-10 25 0.199337 0.0112625 0.00176853 1.90E-10 26 0.794818 0.0111276 0.00174963 2.00E-10 27 28 0.87821 -0.0137423 0.00216441 2.20E-10 29 0.87821 -0.0137423 0.00216441 2.20E-10 30 0.576706 0.00897371 0.00141452 2.20E-10 31 0.72267 0.00994242 0.00156692 2.20E-10 32 33 0.553108 0.00894629 0.00141015 2.20E-10 34 0.512551 0.0089942 0.00141862 2.30E-10 35 0.735808 0.010043 0.00158813 2.60E-10 36 37 0.283869 -0.00986276 0.00155977 2.60E-10 38 0.935497 0.0180623 0.00286715 3.00E-10 39 0.558438 -0.00894625 0.00142037 3.00E-10 40 0.906093 -0.0151579 0.00240898 3.10E-10 41 42 0.235517 0.0104987 0.00167245 3.40E-10 43 0.22119 -0.0106221 0.00169235 3.50E-10 44 0.852214 -0.0123582 0.00197668 4.10E-10 45 46 0.708124 -0.00966485 0.00154958 4.50E-10 47 0.501462 0.00873383 0.00140141 4.60E-10 48 0.623257 -0.00905486 0.00145438 4.80E-10 49 0.547323 -0.0088107 0.00141551 4.80E-10 50 51 0.36595 0.00909179 0.00146249 5.10E-10 52 0.252094 -0.0100337 0.00161534 5.20E-10 53 0.829486 -0.0115552 0.00186101 5.30E-10 54 55 0.627856 0.00900063 0.00145063 5.50E-10 56 0.708451 -0.0095482 0.00154072 5.70E-10 57 0.343693 0.00916326 0.00148225 6.30E-10 58 0.479203 -0.00859803 0.00139942 8.00E-10 59 60 0.672558 0.00933798 0.00151974 8.00E-10 0.22577 0.0102942 0.00167796 8.50E-10

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1 2 0.76914 0.0101915 0.00166266 8.80E-10 3 0.398321 0.00877032 0.00143113 8.90E-10 4 0.896658 0.0141902 0.00232451 1.00E-09 5 6 0.791515 0.0105899 0.00173398 1.00E-09 7 0.962835 -0.023491 0.00384761 1.00E-09 8 0.604907 0.00873564 0.00143338 1.10E-09 9 10 0.808037 0.0108282 0.00177718 1.10E-09 11 0.895237 -0.0139555 0.00229179 1.10E-09 12 Confidential:0.633254 0.00887024 0.00145837 For Review1.20E-09 Only 13 0.948721 0.0193066 0.00317254 1.20E-09 14 15 0.626467 0.00877534 0.00144625 1.30E-09 16 0.388477 0.00868953 0.00143461 1.40E-09 17 0.860357 -0.0122773 0.00202786 1.40E-09 18 19 0.958457 -0.0212245 0.00350972 1.50E-09 20 0.749285 -0.00978511 0.00161906 1.50E-09 21 0.64299 0.00879596 0.00146116 1.70E-09 22 0.781672 -0.0102014 0.00169445 1.70E-09 23 24 0.939168 -0.0176477 0.00292724 1.70E-09 25 0.625064 0.00869839 0.00144586 1.80E-09 26 0.55235 -0.00848341 0.00141026 1.80E-09 27 28 0.701684 -0.00919131 0.00153324 2.00E-09 29 0.850669 -0.011764 0.00196494 2.10E-09 30 0.81462 -0.0109102 0.00182648 2.30E-09 31 0.383726 0.0102212 0.00172477 3.10E-09 32 33 0.383726 0.0102212 0.00172477 3.10E-09 34 0.675262 0.00886383 0.00149881 3.30E-09 35 0.623364 -0.00855375 0.00144694 3.40E-09 36 37 0.921665 -0.0158649 0.00268419 3.40E-09 38 0.9237 -0.0155978 0.00264188 3.50E-09 39 0.864826 0.0121368 0.00205422 3.50E-09 40 0.566915 -0.00834008 0.00141268 3.60E-09 41 42 0.525219 0.00831904 0.0014111 3.70E-09 43 0.549319 -0.00831198 0.00140939 3.70E-09 44 0.484602 0.00823647 0.00140029 4.10E-09 45 46 0.540322 -0.00832494 0.00141551 4.10E-09 47 0.802785 -0.0104052 0.00176934 4.10E-09 48 0.356981 0.00858419 0.00146045 4.20E-09 49 0.899338 -0.0144979 0.00247584 4.70E-09 50 51 0.745591 0.00937821 0.00160653 5.30E-09 52 0.89905 -0.0136092 0.00233533 5.60E-09 53 0.355895 -0.00851275 0.00146314 6.00E-09 54 55 0.416563 -0.00830965 0.00142919 6.10E-09 56 0.398855 -0.00832718 0.00143263 6.20E-09 57 0.395066 0.00830694 0.00143104 6.40E-09 58 0.823184 0.0106994 0.00184273 6.40E-09 59 60 0.261198 0.00935057 0.00161146 6.50E-09 0.399483 0.00830038 0.00143062 6.60E-09

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1 2 0.981257 -0.030147 0.00519975 6.70E-09 3 0.67229 0.008644 0.00149128 6.80E-09 4 0.422104 0.00826633 0.00142691 6.90E-09 5 6 0.759058 -0.00947593 0.00163563 6.90E-09 7 0.540843 -0.00815381 0.0014102 7.40E-09 8 0.900038 -0.0135294 0.00234389 7.80E-09 9 10 0.285863 0.00900156 0.00155995 7.90E-09 11 0.841844 -0.0111229 0.00193299 8.70E-09 12 Confidential:0.741068 -0.0091916 0.00159774 For Review8.80E-09 Only 13 0.637547 0.00839544 0.00146037 9.00E-09 14 15 0.295322 -0.00888158 0.00154644 9.30E-09 16 0.590832 -0.00815867 0.00142095 9.40E-09 17 0.590225 0.00818239 0.00142577 9.50E-09 18 19 0.402699 0.0083571 0.00145745 9.80E-09 20 0.930782 -0.0163924 0.00285925 9.90E-09 21 0.769815 -0.00955906 0.00166864 1.00E-08 22 0.160567 -0.0109168 0.0019097 1.10E-08 23 24 0.373043 -0.00830314 0.00145475 1.10E-08 25 0.831369 -0.0108851 0.00190318 1.10E-08 26 0.618198 -0.00824202 0.00144933 1.30E-08 27 28 0.2779 0.00887429 0.00156422 1.40E-08 29 0.837732 0.0107922 0.00190302 1.40E-08 30 0.777678 0.00954609 0.00168287 1.40E-08 31 0.631534 0.0082093 0.00144953 1.50E-08 32 33 0.804155 0.0100575 0.00177797 1.50E-08 34 0.487454 -0.00804454 0.00142103 1.50E-08 35 0.555071 -0.00799321 0.00141319 1.50E-08 36 37 0.291714 0.00870349 0.0015392 1.60E-08 38 0.975613 -0.0256573 0.00454383 1.60E-08 39 0.646531 0.00829089 0.00146748 1.60E-08 40 0.603803 0.00808755 0.00143229 1.60E-08 41 42 0.391021 0.00807502 0.00143304 1.80E-08 43 0.399349 -0.00806725 0.00143189 1.80E-08 44 0.552146 -0.0079879 0.00141944 1.80E-08 45 46 0.632298 0.00824671 0.00146398 1.80E-08 47 0.614272 0.00806032 0.00143418 1.90E-08 48 0.517188 -0.00788378 0.00140336 1.90E-08 49 0.667322 -0.00833677 0.0014868 2.10E-08 50 51 0.62892 0.00811794 0.0014498 2.20E-08 52 0.82365 -0.0103193 0.00184421 2.20E-08 53 0.255786 -0.00901674 0.00161356 2.30E-08 54 55 0.892937 0.0126892 0.00227288 2.40E-08 56 0.388067 -0.00799938 0.001436 2.50E-08 57 0.685061 -0.00841291 0.00150928 2.50E-08 58 0.716531 0.00866751 0.0015544 2.50E-08 59 60 0.514974 -0.00780358 0.00140196 2.60E-08 0.770482 0.00931829 0.0016779 2.80E-08

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1 2 0.558383 0.00782016 0.00140955 2.90E-08 3 0.315325 -0.00837356 0.00150921 2.90E-08 4 0.290398 -0.00855158 0.00154376 3.00E-08 5 6 0.408838 0.00798275 0.00144004 3.00E-08 7 0.798751 -0.00971214 0.00175212 3.00E-08 8 0.904169 0.0132226 0.00238943 3.10E-08 9 10 0.903565 0.0131142 0.0023713 3.20E-08 11 0.917759 -0.0141143 0.00255396 3.30E-08 12 Confidential:0.865193 -0.0113143 0.00205082 For Review3.40E-08 Only 13 0.890549 0.0124909 0.00226463 3.50E-08 14 15 0.58767 -0.00791789 0.00143674 3.60E-08 16 0.944649 0.0170314 0.00309085 3.60E-08 17 0.230804 0.00924136 0.0016795 3.70E-08 18 19 0.936321 0.0158076 0.00287275 3.70E-08 20 0.783832 -0.00949405 0.00172524 3.70E-08 21 0.443375 -0.00774602 0.00140951 3.90E-08 22 0.5568 0.00777501 0.00141482 3.90E-08 23 24 0.914436 0.0137775 0.00250759 3.90E-08 25 0.682898 -0.00841416 0.00153206 4.00E-08 26 0.213947 -0.00937945 0.00171135 4.20E-08 27 28 0.699952 -0.00837524 0.00152821 4.20E-08 29 0.587339 0.00777281 0.0014188 4.30E-08 30 0.654098 0.00809776 0.00147872 4.30E-08 31 0.631085 0.00794743 0.00145434 4.60E-08 32 33 0.417621 0.00780733 0.00142954 4.70E-08 34 0.664934 0.00807618 0.00148115 5.00E-08 35 0.615818 -0.00790048 0.00144944 5.00E-08 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 10: Genome-wide association study results for early life body size in the UK Biobank (Females only with additional adjustment for month of birth) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs1421085 16 53800954 FTO T C 8 rs543874 1 177889480 SEC16B A G 9 10 rs6738433 2 25159501 DNAJC27 G C 11 rs62106258 2 417167 FAM150B T C 12 rs12992672 Confidential:2 632592 ForTMEM18 ReviewG OnlyA 13 rs12042908 1 74997762 FPGT-TNNI3K A G 14 15 rs12042908 1 74997762 TNNI3K A G 16 rs7132908 12 50263148 FAIM2 G A 17 rs2168711 18 57848531 MC4R T C 18 19 rs12641981 4 45179883 GNPDA2 C T 20 rs148965598 16 19975731 GPR139 A G 21 rs34260097 6 100727703 SIM1 T G 22 rs2206277 6 50798526 TFAP2B C T 23 24 rs8030456 15 68076856 MAP2K5 C T 25 rs2126474 8 76878957 HNF4G G T 26 rs115319174 2 207066474 GPR1 G C 27 28 rs2531991 16 4023553 ADCY9 G A 29 rs10821163 9 96343060 PHF2 G C 30 rs11209943 1 72750500 NEGR1 A G 31 rs3131934 6 30931844 DPCR1 T C 32 33 rs2767486 1 65991203 LEPR A G 34 rs17066856 18 58049656 MC4R T C 35 rs34196306 6 27425644 ZNF184 G C 36 37 rs13254613 8 64804804 YTHDF3 A C 38 rs75782365 6 26408551 BTN3A1 T G 39 rs3749971 6 29342775 OR12D3 G A 40 rs3749971 6 29342775 OR5V1 G A 41 42 rs11039307 11 47611152 C1QTNF4 C T 43 rs7084503 10 2666859 PFKP T C 44 rs7189927 16 28913787 ATP2A1 T C 45 46 rs75001243 7 93216002 GNGT1 C T 47 rs7377083 4 102708997 BANK1 C A 48 rs815610 5 153517178 MFAP3 C G 49 rs34229857 16 67434917 ZDHHC1 C T 50 51 rs10050620 5 63927239 RGS7BP C T 52 rs9551428 13 28618462 FLT3 C T 53 rs41279738 1 110082551 GPR61 T G 54 55 rs796915 6 154304628 OPRM1 C G 56 rs79569013 3 61218295 FHIT T G 57 rs4432271 16 20245283 GP2 C T 58 rs12110721 6 55190480 GFRAL G A 59 60 rs9268235 6 32290208 C6orf10 C T rs2594989 3 11316143 ATG7 C T

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1 2 rs61980008 14 30464716 PRKD1 G A 3 rs962369 11 27734420 BDNF T C 4 rs7268466 20 15810676 MACROD2 C T 5 6 rs7239114 18 45921214 ZBTB7C G A 7 rs11215403 11 115058585 CADM1 G A 8 rs1336486 13 40784814 AL133318.1 T G 9 10 rs3810291 19 47569003 ZC3H4 G A 11 rs9317002 13 59175727 PCDH17 C A 12 rs1775255 Confidential:6 51243035 ForPKHD1 ReviewG OnlyT 13 rs11611246 12 939480 WNK1 G T 14 15 rs7656673 4 30840331 PCDH7 A G 16 rs1446725 2 77222421 LRRTM4 T G 17 rs2275241 9 129370576 LMX1B G A 18 19 rs818219 3 85374589 CADM2 T C 20 rs2303384 11 65640204 EFEMP2 C T 21 rs6001872 22 40703245 TNRC6B A G 22 rs146910503 2 25446473 DNMT3A G A 23 24 rs76971642 10 87575243 GRID1 T C 25 rs4817973 21 40309592 ETS2 G A 26 rs4889630 16 30877544 BCL7C T C 27 28 rs66469746 20 54374063 CBLN4 C A 29 rs12214497 6 10015908 OFCC1 G T 30 rs9293494 5 87204121 TMEM161B T G 31 rs661878 11 29188691 METTL15 A G 32 33 rs11642090 16 81730582 CMIP T C 34 rs818898 9 6970806 KDM4C A G 35 rs10783302 12 49498130 LMBR1L G T 36 37 rs2034963 3 48170802 CDC25A G C 38 rs76152047 3 141183792 ZBTB38 A G 39 rs212540 1 21593117 ECE1 C T 40 rs62515439 8 57165417 CHCHD7 C T 41 42 rs1349641 4 82212652 PRKG2 T G 43 rs1199328 3 138112107 MRAS G A 44 rs994308 20 6603622 BMP2 C T 45 46 rs3936511 5 55860781 AC022431.2 A G 47 rs1865719 14 79923667 NRXN3 A G 48 rs1483153 2 142358477 LRP1B C T 49 rs4235642 5 103818412 NUDT12 A G 50 51 rs13233916 7 138874416 TTC26 C G 52 rs78607331 12 57648644 R3HDM2 C T 53 rs78607331 12 57648644 RP11-123K3.4 C T 54 55 rs12334731 8 11098975 XKR6 G A 56 rs3810304 19 30861683 ZNF536 A G 57 rs2970356 15 90623540 ZNF710 C G 58 rs983949 7 24299013 NPY T G 59 60 rs678653 11 69466737 CCND1 C G rs4932430 15 89363866 ACAN A C

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1 2 rs141127771 6 32632200 HLA-DQB1 G A 3 rs2735556 3 88105360 CGGBP1 T C 4 rs351776 8 28191306 PNOC A C 5 6 rs2187642 12 11855624 ETV6 A C 7 rs4477562 13 54104968 OLFM4 C T 8 rs7305424 12 118399491 KSR2 A T 9 10 rs582220 1 54724762 SSBP3 A G 11 rs62425122 6 166311987 PDE10A G A 12 rs12140153 Confidential:1 62579891 ForINADL ReviewG OnlyT 13 rs6979832 7 127856276 LEP A G 14 15 rs1576655 13 79587841 RBM26 A C 16 rs10798139 1 187714179 PLA2G4A C T 17 rs947088 20 17171373 PCSK2 G T 18 19 rs35202265 13 27986069 GTF3A C T 20 rs72755233 15 100692953 ADAMTS17 G A 21 rs11150745 17 78757626 RPTOR A G 22 rs7005216 8 8547110 CLDN23 G C 23 24 rs17464221 2 188278203 CALCRL C T 25 rs4971239 1 203491150 OPTC G A 26 rs633372 19 49209226 FUT2 G A 27 28 rs4805881 19 33896432 PEPD A C 29 rs12185242 17 47407071 ZNF652 A C 30 rs2629881 3 59778271 FHIT C T 31 rs13190020 5 65012526 SGTB G A 32 33 rs3798544 6 34520267 SPDEF G A 34 rs1546881 1 1660043 SLC35E2 T A 35 rs303753 18 21074922 RIOK3 G A 36 37 rs55959207 2 161016981 ITGB6 A C 38 rs7808296 7 103127620 RELN C T 39 rs9540493 13 66205704 PCDH9 A G 40 rs7759938 6 105378954 LIN28B C T 41 42 rs957512 9 120405705 TLR4 T C 43 rs999493 17 46625519 HOXB3 G A 44 rs1013737 18 937050 ADCYAP1 G C 45 46 rs10784514 12 66452879 LLPH C T 47 rs16982345 19 18500722 GDF15 G A 48 rs2364232 12 93994827 SOCS2 A C 49 rs12309017 12 99677307 ANKS1B G T 50 51 rs7562973 2 219471455 PLCD4 T C 52 rs536436655 1 196321444 KCNT2 A G 53 rs10876457 12 39453689 CPNE8 G A 54 55 rs11863799 16 61933401 CDH8 C T 56 rs12606230 18 52492252 RAB27B T C 57 rs6860760 5 142868379 NR3C1 A G 58 rs242922 17 43946370 SPPL2C A C 59 60 rs815339 1 190116575 BRINP3 T A rs7522014 1 66551759 PDE4B A G

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1 2 rs11111647 12 103945224 STAB2 G A 3 rs76919525 12 50541733 CERS5 T A 4 rs58681688 13 62467001 PCDH20 C G 5 6 rs754635 3 42305131 CCK C G 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 10: Genome-wide association study results for2 early life body size in the UK Biobank (Females only with additional adjustment for month of birth) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP3 on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.598576 -0.0485245 0.0019738 1.90E-133 8 0.795036 -0.0547111 0.00239471 1.60E-115 9 10 0.521298 -0.0404714 0.001938 7.60E-97 11 0.951237 0.0871511 0.00448249 3.40E-84 12 0.171738Confidential:-0.0441612 0.00255972 For1.10E-66 Review Only 13 0.437568 0.0317093 0.00195096 2.10E-59 14 15 0.437568 0.0317093 0.00195096 2.10E-59 16 0.615703 -0.0313259 0.00199022 8.00E-56 17 0.767084 -0.0354041 0.00228462 3.60E-54 18 19 0.566316 -0.0232585 0.00195491 1.20E-32 20 0.861328 0.0322882 0.00282594 3.10E-30 21 0.776199 -0.0252226 0.002317 1.30E-27 22 0.820178 -0.0268812 0.00251988 1.40E-26 23 24 0.772735 0.0233541 0.00230592 4.20E-24 25 0.585837 0.0196292 0.00196711 1.90E-23 26 0.942615 -0.0411294 0.0042018 1.30E-22 27 28 0.252908 -0.0201152 0.0022332 2.10E-19 29 0.658856 -0.0184294 0.00205347 2.80E-19 30 0.396665 -0.017474 0.00197269 8.10E-19 31 0.830748 -0.0227 0.00258069 1.40E-18 32 33 0.798051 -0.02032 0.00241081 3.50E-17 34 0.909035 0.0282168 0.00337884 6.80E-17 35 0.893292 -0.0262304 0.00315682 9.60E-17 36 37 0.653678 -0.0166354 0.00203483 3.00E-16 38 0.892724 -0.0251505 0.0031202 7.60E-16 39 0.878141 -0.0237784 0.00295191 7.90E-16 40 0.878141 -0.0237784 0.00295191 7.90E-16 41 42 0.590985 -0.015642 0.00196413 1.70E-15 43 0.4919 0.0154217 0.00194187 2.00E-15 44 0.352011 0.0160428 0.00202096 2.10E-15 45 46 0.639219 -0.0159246 0.002015 2.70E-15 47 0.570107 -0.0154494 0.00196984 4.40E-15 48 0.442958 0.0152629 0.00194795 4.70E-15 49 0.971245 -0.0446931 0.00577911 1.00E-14 50 51 0.674911 0.0159415 0.00206879 1.30E-14 52 0.373637 0.0152944 0.00200053 2.10E-14 53 0.973821 -0.0464321 0.00608093 2.20E-14 54 55 0.305503 -0.0160243 0.00210369 2.60E-14 56 0.847448 0.0200581 0.0026885 8.60E-14 57 0.131393 -0.0215328 0.00290982 1.40E-13 58 0.825056 -0.0192891 0.00261112 1.50E-13 59 60 0.868509 -0.0206594 0.0028031 1.70E-13 0.178197 0.018651 0.00253376 1.80E-13

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1 2 0.960939 -0.0365843 0.00501162 2.90E-13 3 0.694195 -0.0152652 0.00209833 3.50E-13 4 0.85579 -0.02006 0.00277559 4.90E-13 5 6 0.458018 -0.0141401 0.00195707 5.00E-13 7 0.756934 0.0161581 0.00225401 7.60E-13 8 0.671032 -0.0147231 0.00206183 9.30E-13 9 10 0.324288 -0.0147346 0.0020666 1.00E-12 11 0.484805 -0.0138449 0.00194991 1.20E-12 12 0.523256Confidential:-0.0136589 0.00193994 For1.90E-12 Review Only 13 0.787302 -0.0165831 0.00236399 2.30E-12 14 15 0.598244 -0.0137192 0.00197198 3.50E-12 16 0.587024 0.0135628 0.00196242 4.80E-12 17 0.628401 -0.0137997 0.00200211 5.50E-12 18 19 0.540731 -0.013365 0.00194602 6.50E-12 20 0.358616 0.0137677 0.00201325 8.00E-12 21 0.65096 0.0138922 0.00203328 8.30E-12 22 0.978739 0.0469774 0.00693632 1.30E-11 23 24 0.952802 -0.0309188 0.00458576 1.60E-11 25 0.640498 0.0135634 0.00201906 1.80E-11 26 0.200015 0.0162007 0.00241747 2.10E-11 27 28 0.714246 0.0143313 0.00214903 2.60E-11 29 0.655579 0.0135499 0.0020333 2.70E-11 30 0.764128 0.0151332 0.00228223 3.30E-11 31 0.867001 0.0188906 0.00284965 3.40E-11 32 33 0.626662 -0.0133579 0.00201523 3.40E-11 34 0.31577 0.0138792 0.00210311 4.10E-11 35 0.63514 -0.013223 0.00200988 4.70E-11 36 37 0.350909 0.0134274 0.00204404 5.10E-11 38 0.933595 -0.0250491 0.00390039 1.30E-10 39 0.392503 0.0126875 0.00200119 2.30E-10 40 0.632779 0.012691 0.00200656 2.50E-10 41 42 0.602578 0.0124895 0.00198194 2.90E-10 43 0.191322 0.0154606 0.00245803 3.20E-10 44 0.59559 -0.0123527 0.00197312 3.80E-10 45 46 0.80848 0.0153733 0.00245849 4.00E-10 47 0.367452 -0.0125468 0.00201195 4.50E-10 48 0.219317 -0.0145132 0.00233689 5.30E-10 49 0.620775 0.0123632 0.00199579 5.80E-10 50 51 0.910898 0.0210258 0.00339396 5.80E-10 52 0.955142 -0.028871 0.00466768 6.20E-10 53 0.955142 -0.028871 0.00466768 6.20E-10 54 55 0.415531 0.0123348 0.00199531 6.30E-10 56 0.225294 0.0143145 0.00231879 6.70E-10 57 0.679219 -0.0133161 0.00218771 1.20E-09 58 0.714774 -0.013012 0.00214561 1.30E-09 59 60 0.364406 -0.0122365 0.00201811 1.30E-09 0.520603 0.0118034 0.00195294 1.50E-09

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1 2 0.740656 -0.0156349 0.00260051 1.80E-09 3 0.885004 0.0181398 0.00302217 1.90E-09 4 0.452229 -0.011657 0.00194341 2.00E-09 5 6 0.375754 -0.0118733 0.00199434 2.60E-09 7 0.871693 -0.0171924 0.00291623 3.70E-09 8 0.657948 -0.0120593 0.00204771 3.90E-09 9 10 0.433296 -0.0114819 0.00195829 4.50E-09 11 0.703489 0.0124211 0.00211833 4.50E-09 12 0.906179Confidential:0.0198374 0.00340138 For5.50E-09 Review Only 13 0.503266 -0.0113462 0.00194786 5.70E-09 14 15 0.40433 -0.0117131 0.00201204 5.80E-09 16 0.783017 -0.0137074 0.00235527 5.90E-09 17 0.281924 -0.0125186 0.00215876 6.70E-09 18 19 0.377883 -0.0115917 0.00200292 7.10E-09 20 0.888484 -0.0177781 0.00307233 7.20E-09 21 0.681985 0.0120462 0.00208297 7.30E-09 22 0.521898 0.011211 0.00194613 8.40E-09 23 24 0.710655 0.012296 0.00213693 8.70E-09 25 0.831063 -0.0149227 0.00260288 9.90E-09 26 0.466187 0.0110767 0.00193734 1.10E-08 27 28 0.334453 -0.0116963 0.00205351 1.20E-08 29 0.544476 -0.0110083 0.00194432 1.50E-08 30 0.221491 -0.0131935 0.00233517 1.60E-08 31 0.65376 -0.0114746 0.00203411 1.70E-08 32 33 0.866888 -0.0161306 0.00286017 1.70E-08 34 0.627849 -0.0125829 0.00223915 1.90E-08 35 0.654846 -0.0115271 0.00205177 1.90E-08 36 37 0.573522 0.0109359 0.00194901 2.00E-08 38 0.685093 -0.0116758 0.00208157 2.00E-08 39 0.453952 0.0109681 0.00195439 2.00E-08 40 0.321596 -0.0115913 0.00207272 2.20E-08 41 42 0.669346 0.0115413 0.0020612 2.20E-08 43 0.377882 -0.0112251 0.00200512 2.20E-08 44 0.506587 -0.0108579 0.00193935 2.20E-08 45 46 0.31988 -0.0115738 0.00207363 2.40E-08 47 0.749552 -0.0124401 0.00223753 2.70E-08 48 0.740504 0.0122939 0.00221255 2.80E-08 49 0.746762 -0.0124412 0.00224386 2.90E-08 50 51 0.594729 -0.0110175 0.00198728 3.00E-08 52 0.931672 -0.0213038 0.00384756 3.10E-08 53 0.774673 0.0128489 0.00232395 3.20E-08 54 55 0.675113 0.0113949 0.00206531 3.40E-08 56 0.766539 -0.0126289 0.00229045 3.50E-08 57 0.43438 0.0107675 0.00195483 3.60E-08 58 0.405892 -0.0110957 0.00201465 3.60E-08 59 60 0.49499 -0.0106781 0.00194149 3.80E-08 0.672706 0.0115094 0.00209962 4.20E-08

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1 2 0.791562 0.0130837 0.00239443 4.60E-08 3 0.341868 -0.0113593 0.00207811 4.60E-08 4 0.812761 -0.0136502 0.00249907 4.70E-08 5 6 0.113285 -0.0166227 0.00304611 4.80E-08 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 10: Genome-wide association study results for early life body size in the UK Biobank (Females only with additional adjustment for2 month of birth) 3 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 11: Genome-wide association study results for early life body size in the UK Biobank (Males only with additional adjustment for month of birth) 3 SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 SNP Chromosome Base position Closest gene Effect allele Other allele 7 rs56094641 16 53806453 FTO A G 8 rs374892365 2 633055 TMEM18 A T 9 rs539515 1 177889025 SEC16B A C 10 11 rs6749422 2 25150011 ADCY3 C G 12 rs7132908 Confidential:12 50263148 ForFAIM2 ReviewG OnlyA 13 rs77165542 2 430975 FAM150B C T 14 rs663129 18 57838401 MC4R G A 15 rs4650277 1 74993721 FPGT-TNNI3K A G 16 17 rs4650277 1 74993721 TNNI3K A G 18 rs7190603 16 19928662 GPRC5B T C 19 rs10938398 4 45186139 GNPDA2 G A 20 rs115319174 2 207066474 GPR1 G C 21 rs2012697 1 72819612 NEGR1 T C 22 23 rs62405422 6 50796905 TFAP2B T C 24 rs9568868 13 54107583 OLFM4 G T 25 rs3784710 15 68072458 MAP2K5 T C 26 rs7550711 1 110082886 GPR61 C T 27 rs11030102 11 27681596 BDNF C G 28 29 rs2540031 16 4017567 ADCY9 T A 30 rs1532127 19 47571938 ZC3H4 G A 31 rs41310284 10 102447647 PAX2 C A 32 rs1772143 1 205799987 PM20D1 T A 33 rs10504620 8 77288303 ZFHX4 T C 34 35 rs10968101 9 27772542 LINGO2 G A 36 rs115597956 6 54042871 MLIP G A 37 rs12110721 6 55190480 GFRAL G A 38 rs3817334 11 47650993 MTCH2 C T 39 rs12140153 1 62579891 INADL G T 40 41 rs1775255 6 51243035 PKHD1 G T 42 rs13240802 7 76631109 UPK3B G A 43 rs1412815 13 66208985 PCDH9 A T 44 rs10496885 2 142285767 LRP1B G A 45 46 rs78444298 1 184672098 EDEM3 G A 47 rs75577466 5 60605507 ZSWIM6 G C 48 rs7316962 13 28613993 FLT3 A G 49 rs1321434 20 6624443 BMP2 A G 50 rs7978659 12 49507127 LMBR1L G T 51 52 rs7239114 18 45921214 ZBTB7C G A 53 rs3927084 16 28639047 SULT1A1 A C 54 rs12452089 17 2135002 SMG6 A T 55 rs7306710 12 66376091 HMGA2 T C 56 rs2143975 14 33297398 AKAP6 C G 57 58 rs73898513 20 15806210 MACROD2 C T 59 rs4958361 5 153545587 MFAP3 C G 60 rs2979139 8 8268313 SGK223 A G rs11790060 9 96202932 FAM120AOS T C

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1 2 rs13107325 4 103188709 SLC39A8 C T 3 rs17637472 17 47461433 RP11-81K2.1 G A 4 rs25842 5 66163135 MAST4 C T 5 rs10896348 11 68357368 PPP6R3 T C 6 7 rs9269212 6 32450249 HLA-DRB5 T A 8 rs9880272 3 85687785 CADM2 T G 9 rs2862874 2 58990485 FANCL G T 10 rs61978655 14 30491807 PRKD1 G A 11 rs16120 7 24334724 NPY A G 12 Confidential: For Review Only 13 rs1452991 6 141473363 NMBR G A 14 rs55654862 5 77428253 AP3B1 A G 15 rs12674871 8 9979144 MSRA C T 16 rs2250081 17 74090700 EXOC7 G A 17 rs3212519 5 52351182 ITGA2 A G 18 19 rs7796922 7 33171110 BBS9 A G 20 rs2240071 6 30070932 TRIM31 C G 21 rs3764516 18 52494374 RAB27B A C 22 rs11218734 11 122523246 UBASH3B A G 23 rs7159126 14 93783176 BTBD7 T C 24 25 rs1576655 13 79587841 RBM26 A C 26 rs34722008 4 38659594 AC021860.1 G A 27 rs4688359 3 61198880 FHIT C T 28 rs2693560 6 117523671 VGLL2 A G 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 11: Genome-wide association study results for2 early life body size in the UK Biobank (Males only with additional adjustment for month of birth) SNP - single nucleotide polymorphism identifier, Beta - effect estimate coefficient for SNP3 on body size, SE- standard error of the effect estimate, P - corresponding p -value 4 5 6 Effect allele frequencyBeta Standard Error P 7 0.592926 -0.0462343 0.00208809 1.20E-108 8 0.172138 -0.0423298 0.00272834 2.80E-54 9 0.794706 -0.0387606 0.00253882 1.30E-52 10 11 0.513756 -0.0312963 0.0020506 1.40E-52 12 0.61534Confidential:-0.0317301 0.00210873 For3.60E-51 Review Only 13 0.964633 0.0729779 0.00562539 1.70E-38 14 0.766362 -0.0305794 0.0024294 2.50E-36 15 0.434972 0.0225074 0.00206778 1.40E-27 16 17 0.434972 0.0225074 0.00206778 1.40E-27 18 0.858283 0.0295453 0.00294667 1.20E-23 19 0.564934 -0.0207419 0.00207649 1.70E-23 20 0.942157 -0.0434464 0.00444271 1.40E-22 21 0.40094 -0.0191725 0.00208941 4.50E-20 22 23 0.820351 -0.0219143 0.00267427 2.50E-16 24 0.870238 -0.0248357 0.00308104 7.60E-16 25 0.774324 0.0191519 0.00244802 5.10E-15 26 0.974201 -0.050689 0.0064924 5.80E-15 27 0.740105 -0.0176821 0.00233919 4.10E-14 28 29 0.404794 -0.015752 0.002136 1.60E-13 30 0.317824 -0.0156647 0.00220336 1.20E-12 31 0.899122 0.0241955 0.00343721 1.90E-12 32 0.586983 0.0146266 0.00208391 2.20E-12 33 0.30137 -0.0151614 0.00224006 1.30E-11 34 35 0.522489 -0.0137762 0.00205908 2.20E-11 36 0.945374 -0.0299346 0.00451919 3.50E-11 37 0.826289 -0.0182543 0.00278111 5.30E-11 38 0.59283 -0.0136287 0.00208248 6.00E-11 39 0.905264 0.0234355 0.00358602 6.40E-11 40 41 0.523597 -0.013298 0.00206002 1.10E-10 42 0.249069 0.0165446 0.00261478 2.50E-10 43 0.394462 0.0133337 0.00211405 2.80E-10 44 0.813737 0.0165578 0.00263586 3.30E-10 45 46 0.980678 0.0470926 0.00750673 3.50E-10 47 0.822678 0.0169305 0.00270047 3.60E-10 48 0.453454 0.0129095 0.00206356 4.00E-10 49 0.540081 -0.0127797 0.00205916 5.40E-10 50 0.657854 -0.0133407 0.00216328 7.00E-10 51 52 0.458743 -0.0127591 0.0020767 8.10E-10 53 0.590581 -0.0125861 0.00208799 1.70E-09 54 0.650315 0.0129844 0.00215521 1.70E-09 55 0.478843 0.0124015 0.00206898 2.00E-09 56 0.466424 0.0122643 0.00207061 3.20E-09 57 58 0.877529 -0.018767 0.00318244 3.70E-09 59 0.47209 0.0121046 0.00205412 3.80E-09 60 0.507064 -0.0120869 0.00205763 4.20E-09 0.669266 -0.012826 0.00218263 4.20E-09

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1 2 0.924027 -0.0226565 0.00387919 5.20E-09 3 0.602276 -0.0123691 0.00211764 5.20E-09 4 0.722624 0.0134119 0.00229862 5.40E-09 5 0.723406 0.0133088 0.00228823 6.00E-09 6 7 0.754059 -0.0143663 0.00248596 7.50E-09 8 0.758575 -0.0138413 0.0023977 7.80E-09 9 0.38849 -0.0121111 0.0021138 1.00E-08 10 0.961487 -0.0304861 0.00535128 1.20E-08 11 0.480152 0.01167 0.00205815 1.40E-08 12 Confidential: For Review Only 13 0.627381 -0.0121032 0.00213948 1.50E-08 14 0.762977 0.0136156 0.00241139 1.60E-08 15 0.799049 -0.0143886 0.00256874 2.10E-08 16 0.552294 0.0114821 0.00206556 2.70E-08 17 0.930458 0.0224404 0.00404697 2.90E-08 18 19 0.906001 0.0195934 0.00353093 2.90E-08 20 0.746927 -0.0130884 0.00236113 3.00E-08 21 0.234545 0.0133945 0.00242496 3.30E-08 22 0.742952 -0.0129259 0.00234663 3.60E-08 23 0.717605 0.012566 0.00228015 3.60E-08 24 25 0.403779 -0.011767 0.00213719 3.70E-08 26 0.64646 0.0118004 0.00214942 4.00E-08 27 0.625376 0.0116467 0.00212296 4.10E-08 28 0.371147 0.0115946 0.00212554 4.90E-08 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 11: Genome-wide association study results for early life body size in the UK Biobank (Males only with additional adjustment for month2 of birth) 3 4 5 6 7 8 9 10 11 12 Confidential: For Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 Supplementary Table 12: Genetically determined effect estimates from univariable and multivariable Mendelian randomization analysis 4 5 assessing the effect of both predicted early life and adult body size on 4 disease outcomes 6 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 7 8 Univariable analysis 9 10 Outcome Timepoint nSNPs Beta 11 Early life 279 0.4 12 Coronary Confidential:Artery Disease - Nikpay et al (2015) For Review Only 13 Adulthood 522 0.59 14 Early life 190 0.84 15 Type 2 Diabetes - Morris et al (2012) 16 Adulthood 323 1.15 17 Early life 124 -0.46 18 Breast cancer - Michailidou et al (2017) 19 Adulthood 191 -0.2 20 Early life 66 -0.14 21 Prostate cancer - Schumacher et al (2018) 22 Adulthood 151 -0.12 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 12: Genetically determined effect estimates from3 univariable and multivariable Mendelian randomization analysis 4 assessing the effect of both predicted early life and adult body size on5 4 disease outcomes nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient6 per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 7 8 Univariable analysis Multivariable analysis 9 10 SE P Beta SE P 11 0.06 1.22 x 10-10 0.02 0.09 0.83 12 Confidential: For Review Only -29 -16 13 0.05 6.54 x 10 0.6 0.07 6.48 x 10 14 0.14 3.83 x 10-09 0.15 0.23 0.52 15 -14 -07 16 0.15 1.98 x 10 1.03 0.2 3.96 x 10 17 0.07 3.84 x 10-11 -0.52 0.09 3.92 x 10-09 18 19 0.06 8.04 x 10-04 0.08 0.08 0.32 20 0.1 0.16 0.06 0.14 0.65 21 22 0.07 0.08 -0.14 0.11 0.21 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 Supplementary Table 13: F-statistics for univariable and multivariable Mendelian randomization analyses 4 All values represent F-statistics derived to assess instrument strength in these analyses 5 6 Univariable analysis 7 8 Outcome Early life Adulthood 9 Coronary Artery Disease - Nikpay et al (2015) 30.7 42.35 10 Type 2 Diabetes - Morris et al (2012) 34.15 45.15 11 12 BreastConfidential: cancer - Michailidou et al (2017) For Review31.96 Only 35.74 13 Prostate cancer - Schumacher et al (2018) 26.03 42.6 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 13: F-statistics for univariable and multivariable Mendelian3 randomization analyses 4 5 6 Multivariable analysis 7 8 Early life Adulthood 9 13.63 16 10 13.4 15.25 11 12 Confidential:13.28 14.67 For Review Only 13 8.91 12.19 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 14: Assessment of heterogeneity for all outcomes 3 4 nSNPs - number of genetic variants used as instrumental variables, P - corresponding p -value 5 6 Outcome Q-statistic 7 Coronary Artery Disease - Nikpay et al (2015) 195.5 8 9 Type 2 Diabetes - Morris et al (2012) 176.5 10 Breast cancer - Michailidou et al (2017) 98.4 11 12 ProstateConfidential: cancer - Schumacher et al For(2018) Review Only250.3 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 14: Assessment of heterogeneity for all outcomes2 3 nSNPs - number of genetic variants used as instrumental variables, P - corresponding4 p -value 5 6 nSNPs Critical value P 7 652 710.42 >0.999 8 9 423 469.84 >0.999 10 266 302.89 >0.999 11 12 Confidential:184 214.47 For0.0006 Review Only 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 15: Sensitivity analyses using multivariable MR Egger analysis to assess the effect of both predicted early life and adult body size on 4 3 4 disease outcomes 5 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 6 7 8 9 10 Outcome Timepoint 11 12 Confidential: For Review OnlyEarly life 13 Coronary Artery Disease - Nikpay et al (2015) Adulthood 14 Intercept 15 16 Early life 17 Type 2 Diabetes - Morris et al (2012) Adulthood 18 Intercept 19 Early life 20 21 Breast cancer - Michailidou et al (2017) Adulthood 22 Intercept 23 Early life 24 25 Prostate cancer - Schumacher et al (2018) Adulthood 26 Intercept 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 15: Sensitivity analyses using multivariable 2MR Egger analysis to assess the effect of both predicted early life and adult body size on 4 3 disease outcomes 4 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient5 per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 6 7 8 Multivariable MR Egger analysis Multivariable MR Egger analysis 9 Undirected Positive child body size effect 10 Beta SE P Beta SE P 11 12 0.02Confidential:0.086 0.8 For Review0.04 0.098 Only 0.687 13 0.6 0.074 4.38 x 10-15 0.615 0.082 2.26 x 10-13 14 0.0003 0.0006 0.594 -0.0004 0.0009 0.658 15 16 0.12 0.232 0.613 0.309 0.251 0.22 17 1.05 0.204 3.77 x 10-7 1.206 0.231 2.92 x 10-7 18 -0.002 0.001 0.216 -0.004 0.002 0.118 19 -0.478 0.098 1.85 x 10-6 -0.627 0.11 2.89 x 10-8 20 21 0.087 0.09 0.335 -0.027 0.097 0.783 22 -0.0004 0.001 0.597 0.004 0.001 0.004 23 0.078 0.136 0.565 -0.047 0.148 0.748 24 25 -0.15 0.113 0.186 -0.232 0.123 0.062 26 0.001 0.001 0.246 0.003 0.001 0.079 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 Supplementary Table 15: Sensitivity analyses using multivariable MR Egger analysis to assess the effect of both predicted early life and adult 2body size on 4 3 disease outcomes 4 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding5 p -value 6 7 8 Multivariable MR Egger analysis 9 Positive adult body size effect 10 Beta SE P 11 12 0.045Confidential:0.087 0.605 For Review Only 13 0.792 0.122 1.8 x 10-10 14 -0.002 0.002 0.049 15 16 0.181 0.231 0.435 17 1.344 0.319 3.15 x 10-5 18 -0.003 0.003 0.207 19 -0.501 0.098 6.23 x 10-7 20 21 -0.132 0.148 0.374 22 0.004 0.001 0.065 23 0.043 0.135 0.749 24 25 -0.381 0.187 0.044 26 0.004 0.002 0.111 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 Supplementary Table 16: Univariable and multivariable Mendelian randomization analysis assessing the effect of both predicted early life and adult 4 measures on breast cancer (ER+/ER- cases) 5 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 6 7 8 9 Outcome Timepoint 10 Early life 11 Breast cancer (ER+ cases) - Michailidou et al (2017) 12 Confidential: For Review OnlyAdulthood 13 14 Early life Breast cancer (ER- cases) - Michailidou et al (2017) 15 Adulthood 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 Supplementary Table 16: Univariable and multivariable Mendelian randomization3 analysis assessing the effect of both predicted early life and adult measures on breast cancer (ER+/ER- cases) 4 nSNPs - number of genetic variants used as instrumental variables, effect estimate coefficient5 per standardized unit change in exposure, SE- standard error of the effect estimate, P - corresponding p -value 6 7 8 Univariable analysis Multivariable analysis 9 nSNPs Beta SE P Beta SE P 10 -07 -06 11 124 -0.4 0.07 1,43 x 10 -0.47 0.1 1.19 x 10 12 191 Confidential:-0.18 0.07 5.23 x 10 -03For Review0.09 0.09 Only0.33 13 -10 -07 14 124 -0.56 0.09 6.28 x 10 -0.61 0.12 7.83 x 10 15 191 -0.21 0.09 0.016 0.1 0.11 0.37 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 Figure 1 46 47 711x1347mm (72 x 72 DPI) 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 190 of 192

1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 Figure 2 18 2116x635mm (72 x 72 DPI) 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj Page 191 of 192 BMJ

1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 Figure 3 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj BMJ Page 192 of 192

1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 Figure 4 46 47 1058x1411mm (72 x 72 DPI) 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj