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

Research output: Contribution to journalArticle

596 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 - 27-08-2015

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Inflammatory Bowel Diseases
Population
Inborn Genetic Diseases
Genetic Heterogeneity
Ulcerative Colitis
Gene Frequency
Crohn Disease
Genotype
Genome

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

International Multiple Sclerosis Genetics Consortium, & International IBD Genetics Consortium (2015). Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nature Genetics, 47(9), 979-986. https://doi.org/10.1038/ng.3359
International Multiple Sclerosis Genetics Consortium ; International IBD Genetics Consortium. / Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. In: Nature Genetics. 2015 ; Vol. 47, No. 9. pp. 979-986.
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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.",
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International Multiple Sclerosis Genetics Consortium & International IBD Genetics Consortium 2015, 'Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations', Nature Genetics, vol. 47, no. 9, pp. 979-986. https://doi.org/10.1038/ng.3359

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.

In: Nature Genetics, Vol. 47, No. 9, 27.08.2015, p. 979-986.

Research output: Contribution to journalArticle

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AU - Juyal, Ramesh C.

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AU - Kim, Won Ho

AU - Morris, Andrew P.

AU - Poustchi, Hossein

AU - Newman, William G.

AU - Midha, Vandana

AU - Orchard, Timothy R.

AU - Vahedi, Homayon

AU - Sood, Ajit

AU - Sung, Joseph J.Y.

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AU - Westra, Harm Jan

AU - Yamazaki, Keiko

AU - Yang, Suk Kyun

AU - Barrett, Jeffrey C.

AU - Franke, Andre

AU - Alizadeh, Behrooz Z.

AU - Parkes, Miles

AU - Thelma, B. K.

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International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nature Genetics. 2015 Aug 27;47(9):979-986. https://doi.org/10.1038/ng.3359