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

Jimmy Z Liu; Suzanne van Sommeren; Hailiang Huang; Siew C Ng; Rudi Alberts; Atsushi Takahashi; Stephan Ripke; James C Lee; Luke Jostins; Tejas Shah; Shifteh Abedian; Jae Hee Cheon; Judy Cho; Naser E Dayani; Lude Franke; Yuta Fuyuno; Ailsa Hart; Ramesh C Juyal; Garima Juyal; Won Ho Kim; Andrew P Morris; Hossein Poustchi; William G Newman; Vandana Midha; Timothy R Orchard; Homayon Vahedi; Ajit Sood; Joseph J Y  Sung; Reza Malekzadeh; Harm-Jan Westra; Keiko Yamazaki; Suk-Kyun Yang; International Multiple Sclerosis Genetics Consortium; International IBD Genetics Consortium; Jeffrey C Barrett; Andre Franke; Behrooz Z Alizadeh; Miles Parkes; Thelma Bk; Mark J Daly; Michiaki Kubo; Carl A Anderson; Rinse K Weersma; Craig Mowat

doi:10.1038/ng.3359

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

Jimmy Z Liu, Suzanne van Sommeren, Hailiang Huang, Siew C Ng, Rudi Alberts, Atsushi Takahashi, Stephan Ripke, James C Lee, Luke Jostins, Tejas Shah, Shifteh Abedian, Jae Hee Cheon, Judy Cho, Naser E Dayani, Lude Franke, Yuta Fuyuno, Ailsa Hart, Ramesh C Juyal, Garima Juyal, Won Ho KimAndrew P Morris, Hossein Poustchi, William G Newman, Vandana Midha, Timothy R Orchard, Homayon Vahedi, Ajit Sood, Joseph J Y Sung, Reza Malekzadeh, Harm-Jan Westra, Keiko Yamazaki, Suk-Kyun Yang, International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium, Jeffrey C Barrett, Andre Franke, Behrooz Z Alizadeh, Miles Parkes, Thelma Bk, Mark J Daly, Michiaki Kubo, Carl A Anderson (Lead / Corresponding author), Rinse K Weersma (Lead / Corresponding author), Craig Mowat (Contributing member)

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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.

Original language	English
Pages (from-to)	979-986
Number of pages	8
Journal	Nature Genetics
Volume	47
Issue number	9
Early online date	20 Jul 2015
DOIs	https://doi.org/10.1038/ng.3359
Publication status	Published - Sept 2015

Keywords

Case-Control Studies
Colitis, Ulcerative/genetics
Crohn Disease/genetics
Gene Frequency
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Risk Factors

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Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., Abedian, S., Cheon, J. H., Cho, J., Dayani, N. E., Franke, L., Fuyuno, Y., Hart, A., Juyal, R. C., Juyal, G., ... Mowat, C. (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

@article{72cf0888cca04096a2bc04f14286410f,

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

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.",

keywords = "Case-Control Studies, Colitis, Ulcerative/genetics, Crohn Disease/genetics, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors",

author = "Liu, {Jimmy Z} and {van Sommeren}, Suzanne and Hailiang Huang and Ng, {Siew C} and Rudi Alberts and Atsushi Takahashi and Stephan Ripke and Lee, {James C} and Luke Jostins and Tejas Shah and Shifteh Abedian and Cheon, {Jae Hee} and Judy Cho and Dayani, {Naser E} and Lude Franke and Yuta Fuyuno and Ailsa Hart and Juyal, {Ramesh C} and Garima Juyal and Kim, {Won Ho} and Morris, {Andrew P} and Hossein Poustchi and Newman, {William G} and Vandana Midha and Orchard, {Timothy R} and Homayon Vahedi and Ajit Sood and Sung, {Joseph J Y} and Reza Malekzadeh and Harm-Jan Westra and Keiko Yamazaki and Suk-Kyun Yang and {International Multiple Sclerosis Genetics Consortium} and {International IBD Genetics Consortium} and Barrett, {Jeffrey C} and Andre Franke and Alizadeh, {Behrooz Z} and Miles Parkes and Thelma Bk and Daly, {Mark J} and Michiaki Kubo and Anderson, {Carl A} and Weersma, {Rinse K} and Craig Mowat",

year = "2015",

month = sep,

doi = "10.1038/ng.3359",

language = "English",

volume = "47",

pages = "979--986",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

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Liu, JZ, van Sommeren, S, Huang, H, Ng, SC, Alberts, R, Takahashi, A, Ripke, S, Lee, JC, Jostins, L, Shah, T, Abedian, S, Cheon, JH, Cho, J, Dayani, NE, Franke, L, Fuyuno, Y, Hart, A, Juyal, RC, Juyal, G, Kim, WH, Morris, AP, Poustchi, H, Newman, WG, Midha, V, Orchard, TR, Vahedi, H, Sood, A, Sung, JJY, Malekzadeh, R, Westra, H-J, Yamazaki, K, Yang, S-K, International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium, Barrett, JC, Franke, A, Alizadeh, BZ, Parkes, M, Bk, T, Daly, MJ, Kubo, M, Anderson, CA, Weersma, RK & Mowat, C 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

TY - JOUR

T1 - Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

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 - Dayani, 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 - International Multiple Sclerosis Genetics Consortium

AU - International IBD Genetics Consortium

AU - Barrett, Jeffrey C

AU - Franke, Andre

AU - Alizadeh, Behrooz Z

AU - Parkes, Miles

AU - Bk, Thelma

AU - Daly, Mark J

AU - Kubo, Michiaki

AU - Anderson, Carl A

AU - Weersma, Rinse K

A2 - Mowat, Craig

PY - 2015/9

Y1 - 2015/9

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.

KW - Case-Control Studies

KW - Colitis, Ulcerative/genetics

KW - Crohn Disease/genetics

KW - Gene Frequency

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1038/ng.3359

DO - 10.1038/ng.3359

M3 - Article

C2 - 26192919

SN - 1061-4036

VL - 47

SP - 979

EP - 986

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

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

Abstract

Keywords

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