Meta-analysis of sample-level dbGaP data reveals novel shared genetic link between body height and Crohn’s disease

Abstract

To further explore genetic links between complex traits, we developed a comprehensive framework to harmonize and integrate extensive genotype and phenotype data from the four well-characterized cohorts with the focus on cardiometabolic diseases deposited to the database of Genotypes and Phenotypes (dbGaP). We generated a series of polygenic risk scores (PRS) to investigate pleiotropic effects of loci that confer genetic risk for 19 common diseases and traits on body height, type 2 diabetes (T2D), and myocardial infarction (MI). In a meta-analysis of 20,021 subjects, we identified shared genetic determinants of Crohn’s Disease (CD), a type of inflammatory bowel disease, and body height (p = 5.5 × 10–5). The association of PRS-CD with height was replicated in UK Biobank (p = 1.1 × 10–5) and an independent cohort of 510 CD cases and controls (1.57 cm shorter height per PRS-CD interquartile increase, p = 5.0 × 10−3 and a 28% reduction in CD risk per interquartile increase in PRS-height, p = 1.1 × 10–3, with the effect independent of CD diagnosis). A pathway analysis of the variants overlapping between PRS-height and PRS-CD detected significant enrichment of genes from the inflammatory, immune-mediated and growth factor regulation pathways. This finding supports the clinical observation of growth failure in patients with childhood-onset CD and demonstrates the value of using individual-level data from dbGaP in searching for shared genetic determinants. This information can help provide a refined insight into disease pathogenesis and may have major implications for novel therapies and drug repurposing.

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Data availability

Database of Genotypes and Phenotypes (dbGaP, https://www.ncbi.nlm.nih.gov/gap). MetaCore (Thomson Reuters; https://portal.genego.com). Molecular Signatures Database, MSigDB (http://software.broadinstitute.org/gsea/msigdb).

Code availability

The code is available upon request.

References

  1. Andreassen OA, Djurovic S, Thompson WK, Schork AJ, Kendler KS, O’Donovan MC, Rujescu D, Werge T, van de Bunt M, Morris AP et al (2013) Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. Am J Hum Genet 92:197–209

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJ (2000) Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Gut 46:694–700

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Benjamini Y, Hochberg A (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc 57:289–300

    Google Scholar 

  4. Borrelli O, Bascietto C, Viola F, Bueno de Mesquita M, Barbato M, Mancini V, Bosco S, Cucchiara S (2004) Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Digestive Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver 36:342–347

    CAS  Article  Google Scholar 

  5. Bulik-Sullivan BK, Loh PR, Finucane HK, Ripke S, Yang J, Patterson N, Daly MJ, Price AL, Neale BM (2015a) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291–295

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh PR, ReproGen C, Psychiatric Genomics C, Duncan L, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control, C. et al (2015b) An atlas of genetic correlations across human diseases and traits. Nat Genet 47:1236–1241

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Calenda KA, Schornagel IL, Sadeghi-Nejad A, Grand RJ (2005) Effect of recombinant growth hormone treatment on children with Crohn’s disease and short stature: a pilot study. Inflamm Bowel Dis 11:435–441

    PubMed  Article  PubMed Central  Google Scholar 

  8. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, Clark NR, Ma’ayan A (2013) Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform 14:128

    Article  Google Scholar 

  9. Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, Abecasis GR, Barrett JC, Behrens T, Cho J et al (2011) Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet 7:e1002254

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Dai X, Wiernek S, Evans JP, Runge MS (2016) Genetics of coronary artery disease and myocardial infarction. World J Cardiol 8:1–23

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. de Lange KM, Moutsianas L, Lee JC, Lamb CA, Luo Y, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J, Ji SG et al (2017) Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49:256–261

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  12. Deng Y, Pan W (2017) Testing genetic pleiotropy with GWAS summary statistics for marginal and conditional analyses. Genetics 207:1285–1299

    PubMed  PubMed Central  Article  Google Scholar 

  13. Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GA, Adany R, Aromaa A et al (2010) Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 42:295–302

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Duncan L, Shen H, Gelaye B, Meijsen J, Ressler K, Feldman M, Peterson R, Domingue B (2019) Analysis of polygenic risk score usage and performance in diverse human populations. Nat Commun 10:3328

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Esmaeilzadeh A, Ganji A, Goshayeshi L, Ghafarzadegan K, Afzal Aghayee M, Mosanen Mozafari H, Saadatniya H, Hayatbakhs A, Ghavami Ghanbarabadi V (2016) Adult celiac disease: patients are shorter compared with their peers in the general population. Middle East J Dig Dis 8:303–309

    PubMed  PubMed Central  Article  Google Scholar 

  16. Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OM, Amin N, Kemp JP et al (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44:491–501

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Fox CS, Coady S, Sorlie PD, D’Agostino RB Sr, Pencina MJ, Vasan RS, Meigs JB, Levy D, Savage PJ (2007) Increasing cardiovascular disease burden due to diabetes mellitus: the framingham heart study. Circulation 115:1544–1550

    PubMed  Article  Google Scholar 

  18. Genomes Project, C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA et al (2015) A global reference for human genetic variation. Nature 526:68–74

    Article  CAS  Google Scholar 

  19. Gong S, Xu C, Wang L, Liu Y, Owusu D, Bailey BA, Li Y, Wang K (2017) Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol. Dia Res Clin Pract 126:105–114

    CAS  Article  Google Scholar 

  20. Goodarzi MO (2018) Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol 6(3):223–236

    CAS  PubMed  Article  Google Scholar 

  21. Gottesman O, Drill E, Lotay V, Bottinger E, Peter I (2012) Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk? PLoS ONE 7:e46419

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Grasemann C, Unger N, Hovel M, Arweiler-Harbeck D, Herrmann R, Schundeln MM, Muller O, Schweiger B, Lausch E, Meissner T et al (2017) Loss of functional osteoprotegerin: more than a skeletal problem. J Clin Endocrinol Metab 102:210–219

    PubMed  Article  Google Scholar 

  23. Gratten J, Visscher PM (2016) Genetic pleiotropy in complex traits and diseases: implications for genomic medicine. Genome Med 8:78

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. Harstad EB, Weaver AL, Katusic SK, Colligan RC, Kumar S, Chan E, Voigt RG, Barbaresi WJ (2014) ADHD, stimulant treatment, and growth: a longitudinal study. Pediatrics 134:e935–e944

    PubMed  PubMed Central  Article  Google Scholar 

  25. Helgadottir A, Gretarsdottir S, Thorleifsson G, Hjartarson E, Sigurdsson A, Magnusdottir A, Jonasdottir A, Kristjansson H, Sulem P, Oddsson A et al (2016) Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease. Nat Genet 48:634

    CAS  PubMed  Article  Google Scholar 

  26. Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 44:955–959

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Huang J, Johnson AD, O’Donnell CJ (2011) PRIMe: a method for characterization and evaluation of pleiotropic regions from multiple genome-wide association studies. Bioinformatics 27:1201–1206

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. Hui KY, Fernandez-Hernandez H, Hu J, Schaffner A, Pankratz N, Hsu NY, Chuang LS, Carmi S, Villaverde N, Li X et al (2018) Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease. Sci Transl Med 10:eaai7795

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. Jelenkovic A, Bogl LH, Rose RJ, Kangas AJ, Soininen P, Ala-Korpela M, Kaprio J, Silventoinen K (2013) Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects. Am J Hum Biol Off J Hum Biol Counc 25:465–472

    Article  Google Scholar 

  30. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Klimentidis YC, Chougule A, Arora A, Frazier-Wood AC, Hsu C-H (2015) Triglyceride-increasing alleles associated with protection against type-2 diabetes. PLoS Genet 11:e1005204

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  32. Krapohl E, Euesden J, Zabaneh D, Pingault JB, Rimfeld K, von Stumm S, Dale PS, Breen G, O’Reilly PF, Plomin R (2016) Phenome-wide analysis of genome-wide polygenic scores. Mol Psychiatry 21:1188–1193

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A et al (2016) Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44:W90-97

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Lee JJ, Escher JC, Shuman MJ, Forbes PW, Delemarre LC, Harr BW, Kruijer M, Moret M, Allende-Richter S, Grand RJ (2010) Final adult height of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score. Inflamm Bowel Dis 16:1669–1677

    PubMed  PubMed Central  Article  Google Scholar 

  35. Li C, Yang C, Gelernter J, Zhao H (2014) Improving genetic risk prediction by leveraging pleiotropy. Hum Genet 133:639–650

    PubMed  Article  PubMed Central  Google Scholar 

  36. Liang H, Vallarino C, Joseph G, Manne S, Perez A, Zhang S (2014) Increased risk of subsequent myocardial infarction in patients with type 2 diabetes: a retrospective cohort study using the U.K. General practice research database. Dia care 37:1329–1337

    Article  Google Scholar 

  37. Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P (2015) The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst 1:417–425

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373:234–239

    CAS  PubMed  Article  Google Scholar 

  39. Ligthart S, de Vries PS, Uitterlinden AG, Hofman A, Graoup CIW, Franco OH, Chasman DI, Dehghan A (2015) Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein. PLoS ONE 10:e0118859

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  40. Luo W, Obeidat M, Di Narzo AF, Chen R, Sin DD, Pare PD, Hao K (2016) Airway epithelial expression quantitative trait loci reveal genes underlying asthma and other airway diseases. Am J Respir Cell Mol Biol 54:177–187

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, Junkins H, McMahon A, Milano A, Morales J (2017) The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res 45:D896–D901

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, Hao L, Kiang A, Paschall J, Phan L et al (2007) The NCBI dbGaP database of genotypes and phenotypes. Nat Genet 39:1181–1186

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. Malik S, Ahmed SF, Wilson ML, Shah N, Loganathan S, Naik S, Bourke B, Thomas A, Akobeng AK, Fagbemi A et al (2012) The effects of anti-TNF-alpha treatment with adalimumab on growth in children with Crohn’s disease (CD). J Crohn’s Colitis 6:337–344

    CAS  Article  Google Scholar 

  44. Markowitz J, Grancher K, Rosa J, Aiges H, Daum F (1993) Growth failure in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 16:373–380

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. Mauras N, George D, Evans J, Milov D, Abrams S, Rini A, Welch S, Haymond MW (2002) Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. Metab Clin Exp 51:127–135

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. Mills MC, Rahal C (2019) A scientometric review of genome-wide association studies. Commun Biol 2:9

    PubMed  PubMed Central  Article  Google Scholar 

  47. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson W et al (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363:1211–1221

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. Mouratidou N, Malmborg P, Sachs MC, Askling J, Ekbom A, Neovius M, Smedby KE, Savendahl L, Ludvigsson JF, Olen O (2020) Adult height in patients with childhood-onset inflammatory bowel disease: a nationwide population-based cohort study. Aliment Pharmacol Ther 51:789–800

    PubMed  Article  PubMed Central  Google Scholar 

  49. Nalls MA, Saad M, Noyce AJ, Keller MF, Schrag A, Bestwick JP, Traynor BJ, Gibbs JR, Hernandez DG, Cookson MR et al (2014) Genetic comorbidities in Parkinson’s disease. Hum Mol Genet 23:831–841

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. Nelson CP, Hamby SE, Saleheen D, Hopewell JC, Zeng L, Assimes TL, Kanoni S, Willenborg C, Burgess S, Amouyel P et al (2015) Genetically determined height and coronary artery disease. N Engl J Med 372:1608–1618

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S et al (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506:376–381

    CAS  PubMed  Article  Google Scholar 

  52. Panagiotou OA, Travis RC, Campa D, Berndt SI, Lindstrom S, Kraft P, Schumacher FR, Siddiq A, Papatheodorou SI, Stanford JL et al (2015) A genome-wide pleiotropy scan for prostate cancer risk. Eur Urol 67:649–657

    PubMed  Article  Google Scholar 

  53. Parnanen A, Kaukinen K, Helakorpi S, Uutela A, Lahdeaho ML, Huhtala H, Collin P, Maki M, Kurppa K (2012) Symptom-detected and screen-detected celiac disease and adult height: a large cohort study. Eur J Gastroenterol Hepatol 24:1066–1070

    PubMed  Article  Google Scholar 

  54. Pickrell JK, Berisa T, Liu JZ, Segurel L, Tung JY, Hinds DA (2016) Detection and interpretation of shared genetic influences on 42 human traits. Nat Genet 48:709–717

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. Pierce BL, Ahsan H (2011) Genome-wide “pleiotropy scan” identifies HNF1A region as a novel pancreatic cancer susceptibility locus. Cancer Res 71:4352–4358

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909

    CAS  PubMed  Article  Google Scholar 

  57. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. Sawczenko A, Ballinger AB, Savage MO, Sanderson IR (2006) Clinical features affecting final adult height in patients with pediatric-onset Crohn’s disease. Pediatrics 118:124–129

    PubMed  Article  Google Scholar 

  59. Schwarzer G (2007) Meta: an R package for meta-analysis. R news 7:40–45

    Google Scholar 

  60. Shea J, Agarwala V, Philippakis AA, Maguire J, Banks E, DePristo M, Thomson B, Guiducci C, Onofrio RC, The Myocardial Infarction Genetics, C. et al (2011) Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction. Nat Genet 43:801

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. Silverstein MD, Yunginger JW, Reed CE, Petterson T, Zimmerman D, Li JT, O’Fallon WM (1997) Attained adult height after childhood asthma: effect of glucocorticoid therapy. J Allergy Clin Immunol 99:466–474

    CAS  PubMed  Article  Google Scholar 

  62. Sivakumaran S, Agakov F, Theodoratou E, Prendergast JG, Zgaga L, Manolio T, Rudan I, McKeigue P, Wilson JF, Campbell H (2011) Abundant pleiotropy in human complex diseases and traits. Am J Hum Genet 89:607–618

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  63. Socrates A, Bond T, Karhunen V, Auvinen J, Rietveld C, Veijola J, Jarvelin M-R, O’Reilly P (2017) Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes. bioRxiv 1:203257

    Google Scholar 

  64. Sousa AG, Selvatici L, Krieger JE, Pereira AC (2011) Association between genetics of diabetes, coronary artery disease, and macrovascular complications: exploring a common ground hypothesis. Rev Dia Stud RDS 8:230–244

    Article  Google Scholar 

  65. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M et al (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12:e1001779

    PubMed  PubMed Central  Article  Google Scholar 

  66. Takagawa T, Kitani A, Fuss I, Levine B, Brant SR, Peter I, Tajima M, Nakamura S, Strober W (2018) An increase in LRRK2 suppresses autophagy and enhances Dectin-1-induced immunity in a mouse model of colitis. Sci Transl Med 10:eaan8162

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  67. TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute (2014) Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 371:22–31

    Article  CAS  Google Scholar 

  68. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L (2017) Crohn’s disease. Lancet 389:1741–1755

    PubMed  Article  Google Scholar 

  69. Wang SJ, Yang YH, Lin YT, Yang CM, Chiang BL (2002) Attained adult height in juvenile rheumatoid arthritis with or without corticosteroid treatment. Clin Rheumatol 21:363–368

    PubMed  Article  Google Scholar 

  70. Watkins H, Farrall M (2006) Genetic susceptibility to coronary artery disease: from promise to progress. Nat Rev Genet 7:163

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  71. Weiss B, Skourikhin Y, Modan-Moses D, Broide E, Fradkin A, Bujanover Y (2008) Is adult height of patients with celiac disease influenced by delayed diagnosis? Am J Gastroenterol 103:1770–1774

    PubMed  Article  PubMed Central  Google Scholar 

  72. Zhang J, Peng S, Cheng H, Nomura Y, Di Narzo AF, Hao K (2017) Genetic pleiotropy between nicotine dependence and respiratory outcomes. Sci Rep 7:16907

    PubMed  PubMed Central  Article  CAS  Google Scholar 

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Funding

This work was supported by the National Heart, Lung, And Blood Institute [R01HL125027 to IP and HMC], National Human Genome Research Institute [R01HG010649 to IP and HMC], National Institute on Drug Abuse [R01DA047045 to HMC and IP], National Institute of Diabetes and Digestive and Kidney [U24DK062429 and R01DK106593 to KH], National Institute of Environmental Health Sciences [R01ES029212 to KH]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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KH, IP—conceptualization. KH, IP, IF, HMC, PKC, JSH—data curation. KH, IP, IF, HMC, PKC, JSH, MD—investigation. ADN, KH—methodology and formal analysis. AK, AH, CA—validation and resources. IP, KH, MD—supervision. ADN, IP, KH—original draft preparation. IF, HMC, PKC, JSH, AK, AH, CA, MD—review and editing.

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Correspondence to Ke Hao.

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The study was approved by the Icahn School of Medicine Institutional Review Board.

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Study participants for the Mount Sinai Crohn’s and Colitis Registry were consented using a written informed consent.

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Di Narzo, A., Frades, I., Crane, H.M. et al. Meta-analysis of sample-level dbGaP data reveals novel shared genetic link between body height and Crohn’s disease. Hum Genet (2021). https://doi.org/10.1007/s00439-020-02250-3

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