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High-density mapping of the MHC identifies a shared role for HLA-DRB1∗01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

Lookup NU author(s): Dr John Mansfield

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Abstract

© 2015 Nature America, Inc. All rights reserved. Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1∗01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.

Publication metadata

Author(s): Goyette P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, Ripke S, Gusareva ES, Annese V, Hauser SL, Oksenberg JR, Thomsen I, Leslie S, Daly MJ, Van Steen K, Duerr RH, Barrett JC, McGovern DPB, Schumm LP, Traherne JA, Carrington MN, Kosmoliaptsis V, Karlsen TH, Franke A, Rioux JD, Abraham C, Achkar J-P, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Anderson CA, Andrews JM, Aumais G, Baidoo L, Baldassano RN, Balschun T, Bampton PA, Barclay M, Bayless TM, Bethge J, Bis JC, Bitton A, Brand S, Brant SR, Buning C, Chew A, Cho JH, Cleynen I, Cohain A, Croft A, D'Amato M, Danese S, De Jong D, De Vos M, Denapiene G, Denson LA, Devaney KL, Dewit O, D'Inca R, Dubinsky M, Edwards C, Ellinghaus D, Essers J, Ferguson LR, Festen EA, Fleshner P, Florin T, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Green T, Griffiths AM, Guthery SL, Hakonarson H, Halfvarson J, Hanigan K, Haritunians T, Hart A, Hawkey C, Hayward NK, Hedl M, Henderson P, Hu X, Hui KY, Imielinski M, Ippoliti A, Jonaitis L, Kennedy NA, Khan MA, Kiudelis G, Kugathasan S, Kupcinskas L, Latiano A, Laukens D, Lawrance IC, Lee JC, Lees CW, Leja M, Van Limbergen J, Lionetti P, Liu JZ, Louis E, Mahy G, Mansfield J, Massey D, Mathew CG, Milgrom R, Mitrovic M, Montgomery G, Mowat C, Newman W, Ng A, Ng SC, Evelyn Ng SM, Nikolaus S, Ning K, Nothen M, Oikonomou I, Palmieri O, Parkes M, Phillips A, Ponsioen CY, Potocnik U, Prescott NJ, Proctor DD, Radford-Smith G, Rahier J-F, Raychaudhur S, Regueiro M, Rieder F, Roberts R, Russell RK, Sanderson JD, Sans M, Satsangi J, Schadt EE, Schreiber S, Schumm LP, Scott R, Seielstad M, Sharma Y, Silverberg MS, Simms LA, Skieceviciene J, Spain SL, Steinhart AH, Stempak JM, Stronati L, Sventoraityte J, Targan SR, Taylor KM, Ter Velde A, Theatre E, Torkvist L, Tremelling M, Van Der Meulen A, Van Sommeren S, Vasiliauskas E, Vermeire S, Verspaget HW, Walters T, Wwang K, Wwang M-H, Wweersma RK, Wei Z, Whiteman D, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhang H, Zhang W, Zhao H, Zhao ZZ

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2015

Volume: 47

Issue: 2

Pages: 172-179

Online publication date: 05/01/2015

Acceptance date: 04/12/2014

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://doi.org/10.1038/ng.3176

DOI: 10.1038/ng.3176

PubMed id: 25559196

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