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 language | English |
|---|---|
| Pages (from-to) | 979-986 |
| Number of pages | 8 |
| Journal | Nature Genetics |
| Volume | 47 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2015 Aug 27 |
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All Science Journal Classification (ASJC) codes
- Genetics
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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 journal › Article
TY - JOUR
T1 - Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations
AU - International Multiple Sclerosis Genetics Consortium
AU - International IBD Genetics Consortium
AU - Liu, Jimmy Z.
AU - Van Sommeren, Suzanne
AU - Huang, Hailiang
AU - Ng, Siew C.
AU - Alberts, Rudi
AU - Takahashi, Atsushi
AU - Ripke, Stephan
AU - Lee, James C.
AU - Jostins, Luke
AU - Shah, Tejas
AU - Abedian, Shifteh
AU - Cheon, Jae Hee
AU - Cho, Judy
AU - Daryani, Naser E.
AU - Franke, Lude
AU - Fuyuno, Yuta
AU - Hart, Ailsa
AU - Juyal, Ramesh C.
AU - Juyal, Garima
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.
AU - Malekzadeh, Reza
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.
AU - Daly, Mark J.
AU - Kubo, Michiaki
AU - Anderson, Carl A.
AU - Weersma, Rinse K.
PY - 2015/8/27
Y1 - 2015/8/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84940771118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940771118&partnerID=8YFLogxK
U2 - 10.1038/ng.3359
DO - 10.1038/ng.3359
M3 - Article
C2 - 26192919
AN - SCOPUS:84940771118
VL - 47
SP - 979
EP - 986
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 9
ER -