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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, (författare)
Research Center, Montreal Heart Institute, Montreal QC, Canada
Boucher, Gabrielle, (författare)
Research Center, Montreal Heart Institute, Montreal QC, Canada
Mallon, Dermot, (författare)
Department of Surgery, University of Cambridge, Cambridge, UK; National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
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Ellinghaus, Eva, (författare)
Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany
Jostins, Luke, (författare)
Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK; Christ Church, University of Oxford, Oxford, UK
Huang, Hailiang, (författare)
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA; Broad Institute of MIT and Harvard, Cambridge MA, USA
Ripke, Stephan, (författare)
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA; Broad Institute of MIT and Harvard, Cambridge MA, USA
Gusareva, Elena S., (författare)
Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium; Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium
Annese, Vito, (författare)
Unit of Gastroenterology, IRCCS-CSS (Istituto di Ricovero e Cura a Carattere Scientifico–Casa Sollievo della Sofferenza) Hospital, San Giovanni Rotondo, Italy; Unit of Gastroenterology SOD2 (Strutture Organizzative Dipartimentali), Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, Italy
Hauser, Stephen L., (författare)
Department of Neurology, University of California, San Francisco, USA
Oksenberg, Jorge R., (författare)
Department of Neurology, University of California,San Francisco, USA
Thomsen, Ingo, (författare)
Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany
Leslie, Stephen, (författare)
Murdoch Children's Research Institute, Parkville Vic, Australia; Department of Mathematics and Statistics, University of Melbourne, Melbourne Vic, Australia
Daly, Mark J., (författare)
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA; Broad Institute of MIT and Harvard, Cambridge MA, USA
Van Steen, Kristel, (författare)
Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium; Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium
Duerr, Richard H., (författare)
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh PA, USA; Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh PA, USA
Barrett, Jeffrey C., (författare)
Wellcome Trust Sanger Institute, Hinxton, UK
McGovern, Dermot P. B. (författare)
Schumm, L. Philip, (författare)
Department of Public Health Sciences, University of Chicago, Chicago ILL, USA
Traherne, James A., (författare)
Cambridge Institute for Medical Research, Cambridge, UK; Department of Pathology, University of Cambridge, Cambridge, UK
Carrington, Mary N., (författare)
Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick MD, USA; Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge MA, USA
Kosmoliaptsis, Vasilis, (författare)
Department of Surgery, University of Cambridge, Cambridge, UK; National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
Karlsen, Tom H., (författare)
Research Institute of Internal Medicine, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital (Rikshospitalet), Oslo, Norway; Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital (Rikshospitalet), Oslo, Norway
Franke, Andre, (författare)
Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany
Rioux, John D., (författare)
Research Center, Montreal Heart Institute, Montreal QC, Canada; Faculté de Médecine, Université de Montréal, Montreal QC, Canada
Ellinghaust, E (författare)
Thomsent, I (författare)
Karsen, TH (författare)
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2015
Engelska.
Ingår i: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036. ; 47:2, s. 172-179
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)
NATURVETENSKAP  -- Biologiska vetenskaper -- Genetik (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

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