@article{c3b5a25996c24272adff1c0aeee9bd36,
title = "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",
abstract = "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.",
keywords = "Crohn's disease, Genetic Association Study, ulcerative colitis",
author = "Philippe Goyette and Gabrielle Boucher and Dermot Mallon and Eva Ellinghaus and Luke Jostins and Hailiang Huang and Stephan Ripke and Gusareva, {Elena S.} and Vito Annese and Hauser, {Stephen L.} and Oksenberg, {Jorge R.} and Ingo Thomsen and Stephen Leslie and Daly, {Mark J.} and {Van Steen}, Kristel and Duerr, {Richard H.} and Barrett, {Jeffrey C.} and McGovern, {Dermot P.B.} and Schumm, {L. Philip} and Traherne, {James A.} and Carrington, {Mary N.} and Vasilis Kosmoliaptsis and Karlsen, {Tom H.} and Andre Franke and Rioux, {John D.} and {International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)} and Clara Abraham and Achkar, {Jean Paul} and Tariq Ahmad and Leila Amininejad and Ananthakrishnan, {Ashwin N.} and Vibeke Andersen and Anderson, {Carl A.} and Andrews, {Jane M.} and Guy Aumais and Leonard Baidoo and Baldassano, {Robert N.} and Tobias Balschun and Bampton, {Peter A.} and Murray Barclay and Bayless, {Theodore M.} and Johannes Bethge and Bis, {Joshua C.} and Alain Bitton and Stephan Brand and Brant, {Steven R.} and Carsten Buning and Angela Chew and Cho, {Judy H.} and Isabelle Cleynen and Ariella Cohain and Anthony Croft and Mauro D'Amato and Silvio Danese and {De Jong}, Dirk and {De Vos}, Martine and Goda Denapiene and Denson, {Lee A.} and Devaney, {Kathy L.} and Olivier Dewit and Renata D'Inca and Marla Dubinsky and Cathryn Edwards and David Ellinghaus and Jonah Essers and Ferguson, {Lynnette R.} and Festen, {Eleonora A.} and Philip Fleshner and Tim Florin and Denis Franchimont and Karin Fransen and Richard Gearry and Michel Georges and Christian Gieger and Jurgen Glas and Todd Green and Griffiths, {Anne M.} and Guthery, {Stephen L.} and Hakon Hakonarson and Jonas Halfvarson and Katherine Hanigan and Talin Haritunians and Ailsa Hart and Chris Hawkey and Hayward, {Nicholas K.} and Matija Hedl and Paul Henderson and Xinli Hu and Hui, {Ken Y.} and Marcin Imielinski and Andrew Ippoliti and Laimas Jonaitis and Kennedy, {Nicholas A.} and Khan, {Mohammed Azam} and Gediminas Kiudelis and Subra Kugathasan and Limas Kupcinskas and Anna Latiano and Debby Laukens and Lawrance, {Ian C.} and Lee, {James C.} and Lees, {Charlie W.} and Marcis Leja and {Van Limbergen}, Johan and Paolo Lionetti and Liu, {Jimmy Z.} and Edouard Louis and Gillian Mahy and John Mansfield and Dunecan Massey and Mathew, {Christopher G.} and Raquel Milgrom and Mitja Mitrovic and Grant Montgomery and Craig Mowat and William Newman and Aylwin Ng and Ng, {Siew C.} and {Evelyn Ng}, {Sok Meng} and Susanna Nikolaus and Kaida Ning and Markus Nothen and Ioannis Oikonomou and Orazio Palmieri and Miles Parkes and Anne Phillips and Ponsioen, {Cyriel Y.} and Uros Potocnik and Prescott, {Natalie J.} and Proctor, {Deborah D.} and Graham Radford-Smith and Jean-Francois Rahier and Soumya Raychaudhuri and Miguel Regueiro and Florian Rieder and Rebecca Roberts and Russell, {Richard K.} and Sanderson, {Jeremy D.} and Miquel Sans and Jack Satsangi and Schadt, {Eric E.} and Stefan Schreiber and Schumm, {L. Philip} and Regan Scott and Mark Seielstad and Yashoda Sharma and Silverberg, {Mark S.} and Simms, {Lisa A.} and Jurgita Skieceviciene and Spain, {Sarah L.} and Steinhart, {A. Hillary} and Stempak, {Joanne M.} and Laura Stronati and Jurgita Sventoraityte and Targan, {Stephan R.} and Taylor, {Kirstin M.} and {Ter Velde}, Anje and Emilie Theatre and Leif Torkvist and Mark Tremelling and {Van Der Meulen}, Andrea and {Van Sommeren}, Suzanne and Eric Vasiliauskas and Severine Vermeire and Verspaget, {Hein W.} and Thomas Walters and Kai Wang and Ming-Hsi Wang and Weersma, {Rinse K.} and Zhi Wei and David Whiteman and Cisca Wijmenga and Wilson, {David C.} and Juliane Winkelmann and Xavier, {Ramnik J.} and Sebastian Zeissig and Bin Zhang and Zhang, {Clarence K.} and Hu Zhang and Wei Zhang and Hongyu Zhao and Zhao, {Zhen Z.}",
year = "2015",
month = feb,
doi = "10.1038/ng.3176",
language = "English",
volume = "47",
pages = "172--179",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",
}