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Supplementary Information the 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, METASTROKE consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, & Tylee, D. S. (2018). Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. https://doi.org/10.1002/ajmg.b.32652 Peer reviewed version Link to published version (if available): 10.1002/ajmg.b.32652 Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.b.32652 . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Page 47 of 414 American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Supplementary Text: Genetic Correlations: Psychiatric & Immune Phenotypes - 1 1 2 3 Supplementary Text: Genetic correlations among psychiatric and immune-related phenotypes based on 4 genome-wide association data. 5 1* 1 1 1 1 6 Author List: Daniel S Tylee, $iayin Sun, $onathan L Hess, Muhammad A Tahir, Esha Sharma, Rainer 2 2 3 6 7 7 Malik, -rad.ord - /orrall,0 Andrew $ Le1ine, $eremy $ Martinson, Sergey Ne5entse1, Doug Speed, Annegret 8 9 10 10,11 12-13 16 8 8ischer, Eric Mick, -rian R /alker, Andrew Craw.ord, Struan 8 A Grant, Constantin Polychronakos, 12,17 12,12 12,12 8 18 9 $onathan P -rad.ield, Patrick M A Sleiman, Hakon Hakonarson, E1a Ellinghaus, $ames T Elder, 18,19 20 20 8 21 10 Lam C Tsoi, Richard C Trembath, $onathan N -arker, Andre 8ranke, Abbas Dehghan, The 20andMe 22 11 Research Team, The In.lammation /orking Group o. the CHARGE Consortium, The METASTROKE 12 Consortium o. the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE 13 /orking Group, The Obsessi1e Compulsi1e and Tourette Syndrome /orking Group o. the Psychiatric Genomics 1,20 1 14 Consortium, Stephen V 8araone, and Stephen $ Glatt. 15 1 Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab); Departments o. Psychiatry and 16 -eha1ioral Sciences & Neuroscience and Physiology; SBNC Bpstate Medical Bni1ersity; Syracuse, NC, B S A 17 2 Institute .or Stroke and Dementia Research, Klinikum der Bni1ersität MEnchen, Ludwig-Maximilians-Bniversity 18 (LMB), Munich, Germany 19 0 Departments o. Neurology andFor Public Health Peer Sciences, BniveReviewrsity o. Virginia School o. Medicine, Charlottes1ille, 20 VA, B S A 21 2 Department o. Neurology, Da1id Ge..en School o. Medicine, Bni1ersity o. Cali.ornia Los Angeles, Los Angeles, 22 CA, B S A 23 3 Department o. In.ectious Diseases and Microbiology, Graduate School o. Public Health, Bni1ersity o. Pittsburgh, 24 PA, B S A 25 6 Department o. Medicine, Bniversity o. Cambridge, Cambridge, B K 26 7 Genetics Institute, Bni1ersity College London, London, /C1E 6-T, B K 27 8 Institute o. Clinical Molecular -iology, Christian Albrechts Bni1ersity o. Kiel, Kiel, Germany 28 9 Department o. Fuantitative Health Sciences, Bni1ersity o. Massachusetts Medical School, /orcester, MA, B S A 29 10 -H8 Centre .or Cardio1ascular Science, FueenGs Medical Research Institute, Bni1ersity o. Edinburgh, 30 Edinburgh, EH16 2T$, B K 31 11 School o. Social and Community Medicine, MRC Integrated Epidemiology Bnit, Bni1ersity o. -ristol, -ristol, 32 -S8 2-N, BK 33 12 Center .or Applied Genomics, Division o. Human Genetics, The ChildrenGs Hospital o. Philadelphia, 34 Philadelphia, PA, B S A 35 10 Division o. Endocrinology and Diabetes, The ChildrenGs Hospital o. Philadelphia, Philadelphia, PA, B S A 36 12 Department o. Pediatrics, Perelman School o. Medicine, Bni1ersity o. Pennsyl1ania, Philadelphia, PA, B S A 37 13 Institute o. Diabetes, Obesity and Metabolism, Perelman School o. Medicine, Bni1ersity o. Pennsylvania, 38 Philadelphia, PA, B S A 39 16 Endocrine Genetics Laboratory, Department o. Pediatrics and the Child Health Program o. the Research Institute, 40 McGill Bniversity Health Centre, Montreal, Fuebec, Canada 41 17 Fuantinuum Research LLC, San Diego, CA, B S A 42 18 Department o. Dermatology, Veterans A..airs Hospital, Bniversity o. Michigan, Ann Arbor, Michigan, Bnited 43 States o. America 44 19 Department o. -iostatistics, Bni1ersity o. Michigan, Ann Arbor, Michigan, Bnited States o. America 45 20 Division o. Genetics and Molecular Medicine, KingHs College London, London, BK 46 21 Department o. -iostatistics and Epidemiology, MRC-PHE Centre .or En1ironment and Health, School o. Public 47 Health, Imperial College London 48 22 20andMe, Inc , Mountain View, CA, BSA 49 20 K G $ebsen Centre .or Research on Neuropsychiatric Disorders, Bniversity o. -ergen, -ergen, Norway 50 51 52 53 54 55 56 57 58 59 60 John Wiley & Sons, Inc. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Page 48 of 414 Supplementary Text: Genetic Correlations: Psychiatric & Immune Phenotypes - 2 1 2 3 Correlations among Immune-Inflammatory Phenotypes 4 5 In addition to correlations between psychiatric and immune-related phenotypes, we also 6 7 examined the correlations among the set o. immune-related phenotypes, some o. which ha1e not 8 9 10 pre1iously been examined using the LD score regression (LDSC) method. /e obser1ed se1eral highly 11 12 signi.icant correlations, which are depicted in Supplementary Figure 5, with .ull summary statistics in 13 14 Supplementary Table 2. Speci.ically, thirty-one correlations sur1i1ed family-wise BH correction. 15 16 Among the in.lammatory bowel disorders, celiac disease was positi1ely correlated with CrohnGs 17 18 disease (rg I 0 ,7 J 0.08, uncorrected p = 8.0x10-2), rheumatoid arthritis (rg = 0 ,2 + 0.08, p = 2 ,x10-0), 19 For Peer Review 20 type 1 diabetes (rg I 0 02 J 0.09, p = 6.0x10-2), allergy (rg = 0.19 + 0.07, p = 6.8x10-0), hypothyroidism 21 22 (rg = 0 08 + 0.09, p I 2.0x10-3), and psoriasis (rg = 0 ,0 + 0.09, p = 0.01). CrohnGs disease was 23 24 additionally positi1ely correlated with ulcerati1e colitis (rg I 0 71 J 0.06, p = 3 3x10-06), psoriasis (rg = 25 26 0 02 + 0.07, p = 2 0x10-7), and primary biliary cirrhosis (rg I 0 ,2 J 0.08, p = 1 6x10-0). Ulcerati1e colitis 27 28 was likewise positi1ely correlated with psoriasis (rg = 0 09 + 0.08, p =1 6x10-6) and primary biliary 29 30 -2 31 cirrhosis (rg I 0 02 J 0.09, p = 4.0x10 ), as well as susceptibility pulmonary tuberculosis (rg I 0 02 + 32 33 0.12, p = 0.12) 34 35 Rheumatoid arthritis was .ound to be positi1ely correlated with type 1 diabetes (rg = 0 21 + 0.12, 36 37 p = 2.1x10-0), hypothyroidism (rg = 0 02 + 0.07, p = 7 2x10-6), primary biliary cirrhosis (rg = 0 ,7 + 0.08, 38 39 p = 1 2x10-0), psoriasis (rg I 0.17 + 0.07, p I 0.01), and systemic lupus erythematosus (rg = 0 26 + 0.06, 40 41 p = 1.8x10-10). Allergy was positi1ely correlated with susceptibility to pulmonary tuberculosis (rg = 0 ,2 42 43 J 0.08, p I 8.1x10-0), asthma (rg I 0 79 J 0.02, p = 2 0x10-107), atopic dermatitis (rg = 0 ,3 J 0.07, p = 44 45 2.0x10-2), childhood ear in.ections (rg I 0 ,2 J 0.03, p = 2 :x10-6), CRP (rg I 0.10 + 0.03, p = 5 2x10-0), 46 47 and hypothyroidism (rg I 0 ,0 + 0.03, p = 4 0x10-3). Asthma was positi1ely correlated with atopic 48 49 -7 -2 50 dermatitis (rg = 0 09 + 0.07, p = 1 3x10 ), childhood ear in.ections (rg I 0.13 + 0 02, p = 3 0x10 ), and 51 -2 52 CRP (rg = 0 17 + 0.03, p I 6.0x10 ). 53 54 8inally, hypothyroidism was positi1ely correlated with type 1 diabetes (rg I 0 20 J 0.10, p = 55 56 2 6x10-3), childhood ear in.ections (rg I 0.12 J 0.03, p = 5 2x10-0), and primary biliary cirrhosis (rg I 57 58 59 60 John Wiley & Sons, Inc. Page 49 of 414 American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Supplementary Text: Genetic Correlations: Psychiatric & Immune Phenotypes - 3 1 2 3 0 ,2 + 0.09, p = 7 6x10-0). Primary biliary cirrhosis was additionally positi1ely correlated with psoriasis 4 5 (rg = 0 ,7 + 0.10, p I 5 2x10-0) and systemic lupus erythematosus (rg = 0 62 + 0.08, p = 2 ,x10-10). 6 7 8 9 10 11 12 13 14 15 16 17 18 19 For Peer Review 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 John Wiley & Sons, Inc. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Page 50 of 414 1 2 3 Estimated Heritability based 4 on LD Score Regression GWAS Identifier 5 Method (Color Scaled To 6 Number) 7 8 12_i_iganeph.sumstats 0.142 9 10 14a_i_HAND_dementia.txt.sumstats 0.5305 11 14a_i_HAND_exec.txt.sumstats 0.0705 12 14a_i_HAND_neuronba.txt.sumstats -0.1497 13 14a_i_HAND_speed.txt.sumstats 0.0052 14 14a_i_hiv_control.sumstats 0.2895 15 16 14c_i_tb.sumstats 0.1752 17 21_i_psorarth.sumstats 0.2265 18 22_i_RA_okada.sumstats 0.1386 19 23_i_sarcoid.sumstats For Peer Review 0.9692 20 24_i_sclero.sumstats 0.2049 21 22 28_i_t1d.sumstats 0.1783 23 3_i_allergyany.sumstats 0.0808 24 3_i_asthma.sumstats 0.0685 25 3_i_atopicdermatitis.sumstats 0.0772 26 3_i_childhoodear.sumstats 0.0719 27 28 3_i_crp.sumstats 0.1298 29 3_i_hypothyroid.sumstats 0.0539 30 3_i_pbc.sumstats 0.3716 31 3_i_psoriasis.sumstats 0.8165 32 33 3_i_sle.sumstats
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