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PMID: 26192919 Published · ppublish English Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 47 ·No. 9 ·2015-09-00 ·Pages 979-986

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 JY, Malekzadeh R, Westra HJ, Yamazaki K, Yang SK, International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium, Barrett JC, Alizadeh BZ, Parkes M, Bk T, Daly MJ, Kubo M, Anderson CA, Weersma RK

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.

MeSH Terms
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
Authors & Affiliations
42 authors, click to expand affiliations / ORCID
Liu Jimmy Z
Wellcome Trust Sanger Institute, Hinxton, UK.
van Sommeren Suzanne
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands. | Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Huang Hailiang
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ng Siew C
Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
Alberts Rudi
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
Takahashi Atsushi
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
Ripke Stephan
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lee James C
Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, Cambridge, UK.
Jostins Luke
Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK.
Shah Tejas
Wellcome Trust Sanger Institute, Hinxton, UK.
Abedian Shifteh
Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
Cheon Jae Hee
Yonsei University College of Medicine, Seoul, Korea.
Cho Judy
Icahn School of Medicine, Mount Sinai New York, New York, USA.
Dayani Naser E
Department of Gastroenterology, Emam Hospital, Tehran, Iran.
Franke Lude
Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Fuyuno Yuta
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
Hart Ailsa
IBD Unit, St Mark's Hospital, Harrow, Middlesex, UK.
Juyal Ramesh C
National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, India.
Juyal Garima
Department of Genetics, University of Delhi South Campus, New Delhi, India.
Kim Won Ho
Yonsei University College of Medicine, Seoul, Korea.
Morris Andrew P
Welcome Trust Center for Human Genetics, Oxford U.K. and Department of Biostatistics, University of Liverpool, Liverpool, UK.
Poustchi Hossein
Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
Newman William G
Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Midha Vandana
Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
Orchard Timothy R
St Mary's Hospital, London, UK.
Vahedi Homayon
Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
Sood Ajit
Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
Sung Joseph Y
Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
Malekzadeh Reza
Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
Westra Harm-Jan
Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Yamazaki Keiko
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
Yang Suk-Kyun
Asan Medical Center, University of Ulsan College Medicine, Seoul, Korea.
International Multiple Sclerosis Genetics Consortium
International IBD Genetics Consortium
Barrett Jeffrey C
Wellcome Trust Sanger Institute, Hinxton, UK.
Alizadeh Behrooz Z
Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
Parkes Miles
Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, Cambridge, UK.
Bk Thelma
Department of Genetics, University of Delhi South Campus, New Delhi, India.
Daly Mark J
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kubo Michiaki
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
Anderson Carl A
Wellcome Trust Sanger Institute, Hinxton, UK.
Weersma Rinse K
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
Investigators
217 investigators, click to expand
Abedian Shifteh
Abraham Clara
Achkar Jean-Paul
Ahmad Tariq
Alberts Rudi
Alizadeh Behrooz
Amininejad Leila
Anathakrishnan Ashwin N
Andersen Vibeke
Anderson Carl A
Andrews Jane M
Annese Vito
Aumais Guy
Baidoo Leonard
Baldassano Robert N
Balschun Tobias
Bampton Peter A
Barclay Murray
Barrett Jeffrey C
Bayless Theodore M
Bethge Johannes
Bewshea Claire
Bis Joshua C
Bitton Alain
B K Thelma
Boucher Gabrielle
Brain Oliver
Brand Stephan
Brant Steven R
Büning Carsten
Cheon Jae Hee
Chew Angela
Cho Judy H
Cleynen Isabelle
Cohain Ariella
Cooney Rachel
Croft Anthony
Daly Mark J
D'Amato Muro
Danese Silvio
Daryani Naser Ebrahim
De Jong Dirk
de Lange Katrina M
De Vos Martine
Denapiene Goda
Denson Lee A
Devaney Kathy L
Dewit Olivier
D'Inca Renata
Drummond Hazel E
Dubinsky Marla
Duerr Richard H
Edwards Cathryn
Ellinghaus David
Esaki Motohiro
Essers Jonah
Ferguson Lynnette R
Festen Eleonora A
Fleshner Philip
Florin Tim
Franchimont Denis
Franke Andre
Fransen Karin
Fuyano Yuta
Gearry Richard
Georges Michel
Gieger Christian
Glas Jürgen
Goyette Philippe
Green Todd
Griffiths Anne M
Guthery Stephen L
Hakonarson Hakon
Halfvarson Jonas
Hanigan Katherine
Haritunians Talin
Hart Alisa
Hawkey Chris
Hayward Nicholas K
Hedl Matija
Henderson Paul
Hold Georgina L
Hu Xinli
Huang Hailiang
Hui Ken Y
Imielinski Marcin
Ippoliti Andrew
Jazayeri Omid
Jonaitis Laimas
Jostins Luke
Juyal Garima
Juyal Ramesh Chandra
Kalla Rahul
Karlsen Tom H
Kawaguchi Takaaki
Kennedy Nicholas A
Khan Mohammed Azam
Kim Won Ho
Kitazono Takanari
Kiudelis Gediminas
Kubo Michiaki
Kugathasan Subra
Kupcinskas Limas
Lamb Christopher A
Latiano Anna
Laukens Debby
Lawrance Ian C
Lee James C
Lees Charlie W
Leja Marcis
Lewis Nina
Van Limbergen Johan
Lionetti Paolo
Liu Jimmy Z
Louis Edouard
Luo Yang
Mahy Gillian
Malekzadeh Masoud Mohammad
Malekzadeh Reza
Mansfield John
Marriott Suzie
Massey Dunecan
Mathew Christopher G
Matsui Toshiyuki
McGovern Dermot P B
Midha Vandana
Milgrom Raquel
Mirzaei Samaneh
Mitrovic Mitja
Montgomery Grant W
Motoya Satoshi
Mowat Craig
Newman William G
Ng Aylwin
Ng Siew C
Ng Sok Meng Evelyn
Nikolaus Susanna
Nimmo Elaine R
Ning Kaida
Nöthen Markus
Oikonomou Ioannis
Orchard Timothy R
Palmieri Orazio
Parkes Miles
Phillips Anne
Ponsioen Cyriel Y
Potocnik Urõs
Poustchi Hossein
Prescott Natalie J
Proctor Deborah D
Radford-Smith Graham
Rahier Jean-Francois
Raychaudhuri Soumya
Regueiro Miguel
Rieder Florian
Rioux John D
Ripke Stephan
Roberts Rebecca
Russell Richard K
Sanderson Jeremy D
Sans Miquel
Satsangi Jack
Schadt Eric E
Schreiber Stefan
Schumm L Philip
Scott Regan
Seielstad Mark
Shah Tejas
Sharma Yashoda
Silverberg Mark S
Simmons Alison
Simms Lisa A
Singh Abhey
Skieceviciene Jurgita
Sood Ajit
Spain Sarah L
Steinhart A Hilary
Stempak Joanne M
Stronati Laura
Sung Joseph J Y
Suzuki Yasuo
Sventoraityte Jurgita
Takahashi Atsushi
Takazoe Masakazu
Tanaka Hiroki
Taylor Kirstin M
ter Velde Anje
Theatre Emilie
Torkvist Leif
Tremelling Mark
Uhlig Holm H
Vahedi Homayon
van der Meulen Andrea
van Sommeren Suzanne
Vasiliauskas Eric
Ventham Nicholas T
Vermeire Severine
Verspaget Hein W
Walters Thomas
Wang Kai
Wang Ming-Hsi
Weersma Rinse K
Wei Zhi
Whiteman David
Wijmenga Cisca
Wilson David C
Winkelmann Julianne
Xavier Ramnik J
Yamada Tetsuhiro
Yamazaki Keiko
Zeissig Sebastian
Zhang Bin
Zhang Clarence K
Zhang Hu
Zhang Wei
Zhao Hongyu
Zhao Zhen Z
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.3359
Published
2015-09-00
Epub
2015-00-20
Pages
979-986
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4881818
Subset
IM
Grants
Wellcome Trust · 098017 · United Kingdom
NINDS NIH HHS · R01 NS049477 · United States
NIDDK NIH HHS · P30 DK043351 · United States
NIDDK NIH HHS · U01 DK062429 · United States
Wellcome Trust · 098051 · United Kingdom
Medical Research Council · G0800759 · United Kingdom
Chief Scientist Office · ETM/75 · United Kingdom
Wellcome Trust · 102974 · United Kingdom
Chief Scientist Office · ETM/137 · United Kingdom
Medical Research Council · G0800675 · United Kingdom
NIDDK NIH HHS · U01 DK062420 · United States
Medical Research Council · G0600329 · United Kingdom
Department of Health · NIHR-RP-R3-12-026 · United Kingdom
External Links
PubMed source DOI: 10.1038/ng.3359 PMC Full Text View journal details
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