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Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.

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

Collaborators (217)

Abedian S, Abraham C, Achkar JP, Ahmad T, Alberts R, Alizadeh B, Amininejad L, Anathakrishnan AN, Andersen V, Anderson CA, Andrews JM, Annese V, Aumais G, Baidoo L, Baldassano RN, Balschun T, Bampton PA, Barclay M, Barrett JC, Bayless TM, Bethge J, Bewshea C, Bis JC, Bitton A, B K T, Boucher G, Brain O, Brand S, Brant SR, Büning C, Cheon JH, Chew A, Cho JH, Cleynen I, Cohain A, Cooney R, Croft A, Daly MJ, D'Amato M, Danese S, Daryani NE, De Jong D, de Lange KM, De Vos M, Denapiene G, Denson LA, Devaney KL, Dewit O, D'Inca R, Drummond HE, Dubinsky M, Duerr RH, Edwards C, Ellinghaus D, Esaki M, Essers J, Ferguson LR, Festen EA, Fleshner P, Florin T, Franchimont D, Franke A, Fransen K, Fuyano Y, Gearry R, Georges M, Gieger C, Glas J, Goyette P, Green T, Griffiths AM, Guthery SL, Hakonarson H, Halfvarson J, Hanigan K, Haritunians T, Hart A, Hawkey C, Hayward NK, Hedl M, Henderson P, Hold GL, Hu X, Huang H, Hui KY, Imielinski M, Ippoliti A, Jazayeri O, Jonaitis L, Jostins L, Juyal G, Juyal RC, Kalla R, Karlsen TH, Kawaguchi T, Kennedy NA, Khan MA, Kim WH, Kitazono T, Kiudelis G, Kubo M, Kugathasan S, Kupcinskas L, Lamb CA, Latiano A, Laukens D, Lawrance IC, Lee JC, Lees CW, Leja M, Lewis N, Van Limbergen J, Lionetti P, Liu JZ, Louis E, Luo Y, Mahy G, Malekzadeh MM, Malekzadeh R, Mansfield J, Marriott S, Massey D, Mathew CG, Matsui T, McGovern DP, Midha V, Milgrom R, Mirzaei S, Mitrovic M, Montgomery GW, Motoya S, Mowat C, Newman WG, Ng A, Ng SC, Ng SM, Nikolaus S, Nimmo ER, Ning K, Nöthen M, Oikonomou I, Orchard TR, Palmieri O, Parkes M, Phillips A, Ponsioen CY, Potocnik U, Poustchi H, Prescott NJ, Proctor DD, Radford-Smith G, Rahier JF, Raychaudhuri S, Regueiro M, Rieder F, Rioux JD, Ripke S, Roberts R, Russell RK, Sanderson JD, Sans M, Satsangi J, Schadt EE, Schreiber S, Schumm LP, Scott R, Seielstad M, Shah T, Sharma Y, Silverberg MS, Simmons A, Simms LA, Singh A, Skieceviciene J, Sood A, Spain SL, Steinhart AH, Stempak JM, Stronati L, Sung JJ, Suzuki Y, Sventoraityte J, Takahashi A, Takazoe M, Tanaka H, Taylor KM, ter Velde A, Theatre E, Torkvist L, Tremelling M, Uhlig HH, Vahedi H, van der Meulen A, van Sommeren S, Vasiliauskas E, Ventham NT, Vermeire S, Verspaget HW, Walters T, Wang K, Wang MH, Weersma RK, Wei Z, Whiteman D, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Yamada T, Yamazaki K, Zeissig S, Zhang B, Zhang CK, Zhang H, Zhang W, Zhao H, Zhao ZZ.

Author information

1
Wellcome Trust Sanger Institute, Hinxton, UK.
2
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
3
Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
4
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
5
Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
6
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
7
Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, Cambridge, UK.
8
Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK.
9
Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
10
Yonsei University College of Medicine, Seoul, Korea.
11
Icahn School of Medicine, Mount Sinai New York, New York, USA.
12
Department of Gastroenterology, Emam Hospital, Tehran, Iran.
13
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
14
IBD Unit, St Mark's Hospital, Harrow, Middlesex, UK.
15
National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, India.
16
Department of Genetics, University of Delhi South Campus, New Delhi, India.
17
Welcome Trust Center for Human Genetics, Oxford U.K. and Department of Biostatistics, University of Liverpool, Liverpool, UK.
18
Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
19
Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
20
St Mary's Hospital, London, UK.
21
Asan Medical Center, University of Ulsan College Medicine, Seoul, Korea.
22
Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
#
Contributed equally

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.

PMID:
26192919
PMCID:
PMC4881818
DOI:
10.1038/ng.3359
[Indexed for MEDLINE]
Free PMC Article

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