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Supplementary Figure 1. Summary of Overall Study Design and Workflow for Meta-Analyses. All Numbers Provided Represent the Maxim

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Supplementary Figure 1. Summary of Overall Study Design and Workflow for Meta-Analyses. All Numbers Provided Represent the Maxim Supplementary Figure 1. Summary of overall study design and workflow for meta-analyses. All numbers provided represent the maximum number specific for that trait (BMI-red, WCadjBMI-blue, and WHRadjBMI-green) and strata (EUR-European descent participants, nonEUR-excluding European descent participants). Three studies provided GWAS data for EUR and nonEUR participants. Supplementary Figure 2. Summary plots of discovery meta-analysis for Approach 1 primary meta-analyses. (a) Manhattan plot showing the loci identified in Approach 1 in primary meta-analyses, used to identify significant main effects loci (SNPadjSMK), in the primary meta-analyses association –log10P-values for BMI-red, WCadjBMI-blue, and WHRadjBMI-green; (b) Manhattan plot showing the loci identified in Approach 1 excluding known regions +/- 500 kb and labeled with the nearest gene to the index SNP; (c) QQ-plot showing the Approach 1 P-values as observed against those expected under the null for each phenotypes separately (colored); (d) QQ-plot for Approach 1 after excluding known association regions. *PSMB10 locus is >500 +/- kb from previously identified index SNPs, but is not independent of known GWAS signals. Supplementary Figure 3. Regional association plots for Approach 1 primary meta-analyses. Regional association plots for all novel loci identified in Approach 1 (SNPadjSMK) in primary meta-analyses for BMI: (a) rs10929925, (b) rs6794880; WCadjBMI: (c) rs17396340, (d) rs6743226, (e) rs4378999, (f) rs7697556, (g) rs10269774, (h) rs6470765, (i) rs9409082, (j) rs6012558; and WHRadjBMI: (k) rs1049281, and ordered as they appear in Table 1. LD has been calculated using the combined ancestries from the 1000 Genomes Phase 1 reference panel. For comparison, each plot highlights the p-value for the tag SNP in Approach 1 (PadjSMK), Approach 2 (Pjoint), Approach 3 (Pint), current smokers (PSMK), and in nonsmokers (PnonSMK). a. BMI: rs10929925 −Approach 1 2 10 r 100 0.8 0.6 0.4 8 0.2 80 ● R ecombination rate ecombination rate 6 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 Coronary artery calcification Chronic kidney disease s disease LINC01248 LINC01105 LINC01247 SOX11 LOC400940 5.8 6 6.2 6.4 6.6 Position on chr2 (Mb) b. BMI: rs6794880 −Approach 1 10 r2 100 0.8 0.6 0.4 8 0.2 80 R ecombination rate ecombination rate 6 60 ● value) − (p 10 ( log cM − / 4 40 Mb ) 2 20 0 0 Obesity−related traits Brain structure LINC00971 84 84.2 84.4 84.6 84.8 Position on chr3 (Mb) c. WCadjBMI: rs17396340 − Approach 1 r2 100 10 0.8 0.6 ● 0.4 80 8 0.2 R ecombination rate ecombination rate 60 6 value) − (p 10 ( log cM − 40 / 4 Mb ) 2 20 0 0 Alcohol dependence (age at onset) PIK3CD CTNNBIP1 NMNAT1 UBE4B KIF1B APITD1 PEX14 CLSTN1 LZIC RBP7 PGD DFFA CASZ1 APITD1−CORT CORT 9.8 10 10.2 10.4 10.6 Position on chr1 (Mb) d. WCadjBMI: rs6743226 − Approach 1 r2 100 10 0.8 0.6 ● 0.4 80 0.2 8 R ecombination rate ecombination rate 60 6 value) − (p 10 ( log cM − 40 / 4 Mb ) 20 2 0 0 Height Brain structure Height Height HIPadjBMI Height KIF1A C2orf54 SNED1 PASK ANO7 SEPT2 STK25 BOK ATG4B ING5 AGXT LOC200772 MTERFD2 HDLBP FARP2 BOK−AS1 DTYMK GAL3ST2 PPP1R7 THAP4 D2HGDH 241.8 242 242.2 242.4 242.6 Position on chr2 (Mb) e. WCadjBMI: rs4378999 − Approach 1 10 r2 100 0.8 0.6 0.4 8 0.2 80 R ● ecombination rate 6 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 Height Height MIR4787 MANF RAD54L2 DOCK3 VPRBP TEX264 RBM15B 50.8 51 51.2 51.4 51.6 Position on chr3 (Mb) f. WCadjBMI: rs7697556 − Approach 1 r2 100 0.8 10 0.6 0.4 ● 80 0.2 8 R ecombination rate ecombination rate 60 6 value) − (p 10 ( log cM − 40 / Mb 4 ) 20 2 0 0 Metabolite levels HIPadjBMI Height Height Lipid metabolism phenotypes ADAMTS3 COX18 ANKRD17 73.2 73.4 73.6 73.8 74 Position on chr4 (Mb) g. WCadjBMI: rs10269774 − Approach 1 10 r2 100 0.8 0.6 8 0.4 80 0.2 R ● ecombination rate 6 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 Height Height Height 1 GWAS hit Height omitted Height HIPadjBMI CYP51A1 ANKIB1 GATAD1 RBM48 CDK6 SAMD9 LRRD1 KRIT1 PEX1 LOC101927497 MGC16142 FAM133B FAM133DP 91.8 92 92.2 92.4 92.6 Position on chr7 (Mb) h. WCadjBMI: rs6470765 − Approach 1 10 r2 100 0.8 0.6 0.4 8 80 0.2 R ecombination rate ecombination rate 6 ● 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 HIPadjBMI Height Inflammatory bowel disease Height LINC00977 GSDMC FAM49B ASAP1 MIR5194 ASAP1−IT2 130.4 130.6 130.8 131 131.2 Position on chr8 (Mb) i. WCadjBMI: rs9409082 − Approach 1 10 r2 100 0.8 0.6 0.4 8 80 0.2 ● ●● R ecombination rate ecombination rate 6 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 Menarche (age at onset) Height Menarche (age at onset) Height 2 GWAS hits Menarche and menopause (age at onset) omitted Menarche (age at onset) Menarche (age at onset) FKTN MIR8081 TAL2 TMEM38B LOC100996590 108.6 108.8 109 109.2 109.4 Position on chr9 (Mb) j. WCadjBMI: rs6012558 − Approach 1 10 r2 100 0.8 0.6 8 0.4 80 0.2 ● R ecombination rate ecombination rate 6 60 value) − (p 10 ( log cM − 4 40 / Mb ) 2 20 0 0 QT interval Obesity−relat Height Height PREX1 ARFGEF2 STAU1 DDX27 KCNB1 LOC102723483 ZNFX1 CSE1L ZFAS1 SNORD12C SNORD12B SNORD12 47.2 47.4 47.6 47.8 48 Position on chr20 (Mb) k. WHRadjBMI: rs1049281 − Approach 1 10 100 r2 0.8 ● 8 0.6 80 R 0.4 ecombination rate 0.2 6 60 value) − (p 10 ( log 4 40 cM − / Mb ) 2 20 0 0 Height Diastolic blood pressure Renal function−related traits (eGRFcrea) Height Systolic blood pressure 20 GWAS hits Pubertal anthropometrics Height omitted Renal function−related traits (sCR) Hematology traits Menopause (age at onset) DDR1 MUC21 HCG22 PSORS1C2 HLA−C HLA−B HCP5 MCCD1 AIF1 LY6G5C MIR4640 MUC22 C6orf15 HCG27 MIR6891 HCG26 NFKBIL1 MIR6832 LY6G6F GTF2H4 PSORS1C1 MICA MICB LTA BAG6 LY6G6E VARS2 CDSN DDX39B PRRC2A LY6G6D SFTA2 CCHCR1 ATP6V1G2−DDX39B APOM C6orf25 8 genes DPCR1 TCF19 SNORD117 C6orf47 CLIC1 omitted POU5F1 SNORD84 GPANK1 MSH5 PSORS1C3 ATP6V1G2 CSNK2B VWA7 TNF LY 6 G 5 B LTB ABHD16A 30.8 31 31.2 31.4 31.6 Position on chr6 (Mb) Supplementary Figure 4. Summary plots of discovery meta-analysis for Approach 2 primary meta-analyses. (a) Manhattan plot showing the loci identified in Approach 2 in primary meta-analyses, used to identify significant joint main+interaction effects loci (SNPjoint), in the primary meta-analyses association –log10P-values for BMI-red, WCadjBMI-blue, and WHRadjBMI-green; (b) Manhattan plot showing the loci identified in Approach 2 excluding known regions +/- 500 kb and labeled with the nearest gene to the index SNP; (c) QQ-plot showing the Approach 2 P-values as observed against those expected under the null for each phenotypes separately (colored); (d) QQ-plot for Approach 2 after excluding known association regions. Supplementary Figure 5. Regional association plots for Approach 2 primary meta-analyses. Regional association plot for all novel loci identified in Approach 2 (SNPjoint) in the primary meta-analyses for BMI: (a) rs10929925, (b) rs13069244; WCadjBMI: (c) rs17396340, (d) rs6743226, (e) rs7697556, (f) rs9408815, and WHRadjBMI: (g) rs1049281, and ordered as they appear in Table 1. LD has been calculated using the combined ancestries from the 1000 Genomes Phase 1 reference panel. For comparison, each plot highlights the p-value for the tag SNP in Approach 1 (PadjSMK), Approach 2 (Pjoint), Approach 3 (Pint), current smokers (PSMK), and in nonsmokers (PnonSMK). a. BMI: rs10929925 − Approach 2 2 10 r 100 0.8 0.6 0.4 8 0.2 80 ●● R ● ecombination rate ecombination rate ● ●● ●●●● ● ● 6 ● 60 ●● ● ● ● ● value) − ● ● (p ● 10 ● ● ( log ● ● cM − 4 ● 40 / Mb ● ● ● ) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●●● ● ● ●● ● ● ● ● ● ● ●● ● ●● ●● ● ● ● ● ● ● 2 ● ● ● ● ● ● ●●● 20 ●● ●●● ● ●● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●●● ● ●●● ● ● ●● ●●● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ●● ● ● ● ● ●● ●● ● ●● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ●● ● ● ● ● ●● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ●●●●● ● ● ● ● ● ●●●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ●● ●●● ● ●●● ● ● ● ● ●● ● ● ● ● ●● ● ●●● ● ● ● ●● ● ● ●● ● ● ● ● ● ●●● ● ●● ●● ● ● ●●● ●● ●●●● ● ● ● ● ● ● ● ●●● ● ●● ● ● ● ● ●●●●● ● ● ● ●● ●● ● ● ● ● ● ● ●● ● ●●● ● ● ● ● ● ●●● ● ● ● ● ● ●●●● ●●●● ●● ●● ● ●● ● ● ●● ● ● ● ● ● ● ●●●● ●● ● ● ●● ●●● ● ● ●● ●●● ● ●●● ● ●● ● ●●●● ● ●●● ● ● ●● ● ● ● ● ● ●● ●●●●●●● ● ● ● ●● ● ●●●●● ●●●● ● ●●●●●●●●●●● ● ●●● ● ● ● ● ● ●●● ● ●● ●●● ● ● ● ● ● ●●● ● ● ● ● ●●●●●●● ●● ●●● ●● ● ● ●●● ●●● ● ● ● ● ● ● ●●●●●●●●● ●● ● ●●●● ● ●● ● ● ● ●●●●●● ●● ● ● ● ●●● ● ●● ●●●● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ●●● ● ● ● ●● ●●● ●●●● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ●● ● ●●●●●● ● ● ● ●●● ●● ●● ●● ● ● ●●●● ●● ● ●● ● ●● ● ● ●● ●●●● ● ● ● ● ● ●● ●●●●● ● ● ●●● ●●● ● ● ● ●●●●●●●● ● ● ● ● ● ● ●● ●● ●●● ●● ● ●● ●●● ● ● ●●●● ● ●● ● ● ● ● ● ●● ● ● ● ● ●●●● ●●●● ● ● ●●● ● ●●●●●●●●● ●●●● ● ● ●●● ● ● ● ●● ● ● ●● ● ● ● ●●● ●●●●● ●● ● ●●●● ●● ●●●●●● ● ●●● ● ● ● ● ● ● ● ●● ●●●● ● ●●● ● ●● ● ●● ●● ●●● ● ● ● ● ● ● ●● ●●●●●● ● ● ●● ● ● ● ●●● ●● ●●● ●●●● ●●● ● ●●● ● ●● ● ● ● ●● ●●● ●●●●● ●● ● ●● ●● ● ●● ● ●●●●●●●●● ●● ●●●●●● ●●● ● ●● ● ●●● ● ●● ● ●● ●●●●● ●● ● ●●●● ● ●●●● ●● ● ● ●●●● ●● ●●●●●●● ●● ●●● ● ● ●●● ●● ●●● ● ● ●● ●● ●●●●●●●●●● ●●●●●●●●● ● ●● ●● ●● 0 ● ● ● ● ●● ●● ●● ● ●●● ●●●●●●●●●●● ● ● ● ● ●●●●● ● ● ● ●●●● ●●● ● ● ● ● ● ● ● ● ●●●● ● ●●●●●●●●● ●●●●●●●●● ●● ●●●● ● ●●●●● 0 Coronary artery calcification Chronic kidney disease s disease LINC01248 LINC01105 LINC01247 SOX11 LOC400940 5.8 6 6.2 6.4 6.6 Position on chr2 (Mb) b. BMI: rs13069244 − Approach 2 10 r2 100 0.8 0.6 0.4 8 0.2 80 ●● R ecombination rate ecombination rate 6 ● 60 ● ● ● ● ● ● value) − (p ● 10 ( log cM −
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