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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.
Goyette, Philippe; Boucher, Gabrielle; Mallon, Dermot; Ellinghaus, Eva; Jostins, Luke; Huang, Hailiang; Ripke, Stephan; Gusareva, Elena S; Annese, Vito; Hauser, Stephen L; Oksenberg, Jorge R; Thomsen, Ingo; Leslie, Stephen; Daly, Mark J; Van Steen, Kristel; Duerr, Richard H; Barrett, Jeffrey C; McGovern, Dermot P B; Schumm, L Philip; Traherne, James A; Carrington, Mary N; Kosmoliaptsis, Vasilis; Karlsen, Tom H; Franke, Andre; Rioux, John D.
Affiliation
  • Goyette P; Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
  • Boucher G; Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
  • Mallon D; 1] Department of Surgery, University of Cambridge, Cambridge, UK. [2] National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
  • Ellinghaus E; Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
  • Jostins L; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK. [2] Christ Church, University of Oxford, St Aldates, UK.
  • Huang H; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Ripke S; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Gusareva ES; 1] Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium. [2] Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
  • Annese V; 1] Unit of Gastroenterology, IRCCS-CSS (Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza) Hospital, San Giovanni Rotondo, Italy. [2] Unit of Gastroenterology SOD2 (Strutture Organizzative Dipartimentali), Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, It
  • Hauser SL; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Oksenberg JR; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Thomsen I; Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
  • Leslie S; 1] Murdoch Children's Research Institute, Parkville, Victoria, Australia. [2] Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
  • Daly MJ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Van Steen K; 1] Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium. [2] Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
  • Duerr RH; 1] Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. [2] Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
  • Barrett JC; Wellcome Trust Sanger Institute, Hinxton, UK.
  • McGovern DP; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Schumm LP; Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA.
  • Traherne JA; 1] Cambridge Institute for Medical Research, Cambridge, UK. [2] Department of Pathology, University of Cambridge, Cambridge, UK.
  • Carrington MN; 1] Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. [2] Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge, Massachusetts, USA.
  • Kosmoliaptsis V; 1] Department of Surgery, University of Cambridge, Cambridge, UK. [2] National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
  • Karlsen TH; 1] Research Institute of Internal Medicine, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. [2] Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division o
  • Franke A; Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
  • Rioux JD; 1] Research Center, Montreal Heart Institute, Montreal, Quebec, Canada. [2] Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada.
Nat Genet ; 47(2): 172-9, 2015 Feb.
Article in En | MEDLINE | ID: mdl-25559196
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inflammatory Bowel Diseases / Chromosome Mapping / Polymorphism, Single Nucleotide / HLA-DRB1 Chains / Major Histocompatibility Complex Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2015 Document type: Article Affiliation country: Canada Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inflammatory Bowel Diseases / Chromosome Mapping / Polymorphism, Single Nucleotide / HLA-DRB1 Chains / Major Histocompatibility Complex Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2015 Document type: Article Affiliation country: Canada Country of publication: United States