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.

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

    Research output: Contribution to journalArticlepeer-review


    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.
    Original languageEnglish
    JournalNature Genetics
    Issue number2
    Publication statusPublished - Feb 2015


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