Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium

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955 Citations (Scopus)

Abstract

Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

Original languageEnglish
Pages (from-to)979-986
Number of pages8
JournalNature Genetics
Volume47
Issue number9
DOIs
Publication statusPublished - 2015 Aug 27

Bibliographical note

Funding Information:
R.K.W. is supported by a VIDI grant (016.136.308) from the Netherlands Organization for Scientific Research (NWO) and the Broad Medical Research Program of the Broad Foundation (IBD-0318). L.F. is supported by the Netherlands Organization for Scientific Research (NWO), through NWO VENI grant 916.10.135 and NWO VIDI grant 917.14.374. The research leading to these results has received funding from the European Community’s Health Seventh Framework Programme (FP7/2007–2013) under grant agreement 259867. T.B.K. is supported by Centre of Excellence grant BT/01/COE/07/UDSC/2008 from the Department of Biotechnology of the government of India (New Delhi, India). The collection of Iranian samples has been supported by the Tehran University of Medical Sciences, Iran. UK case collections were supported by the National Association for Colitis and Crohn’s Disease, the Wellcome Trust, the Medical Research Council UK and the Peninsular College of Medicine and Dentistry, Exeter. We also acknowledge National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy’s and St Thomas’ NHS Trust/King’s College London and to Addenbrooke’s Hospital/University of Cambridge School of Clinical Medicine. A.P.M. is supported by the Wellcome Trust under award WT098017. J.Z.L., T.S., J.C.B. and C.A.A. are supported by the Wellcome Trust (098051).

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Genetics

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