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Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
Ji, Sun-Gou; Juran, Brian D; Mucha, Sören; Folseraas, Trine; Jostins, Luke; Melum, Espen; Kumasaka, Natsuhiko; Atkinson, Elizabeth J; Schlicht, Erik M; Liu, Jimmy Z; Shah, Tejas; Gutierrez-Achury, Javier; Boberg, Kirsten M; Bergquist, Annika; Vermeire, Severine; Eksteen, Bertus; Durie, Peter R; Farkkila, Martti; Müller, Tobias; Schramm, Christoph; Sterneck, Martina; Weismüller, Tobias J; Gotthardt, Daniel N; Ellinghaus, David; Braun, Felix; Teufel, Andreas; Laudes, Mattias; Lieb, Wolfgang; Jacobs, Gunnar; Beuers, Ulrich; Weersma, Rinse K; Wijmenga, Cisca; Marschall, Hanns-Ulrich; Milkiewicz, Piotr; Pares, Albert; Kontula, Kimmo; Chazouillères, Olivier; Invernizzi, Pietro; Goode, Elizabeth; Spiess, Kelly; Moore, Carmel; Sambrook, Jennifer; Ouwehand, Willem H; Roberts, David J; Danesh, John; Floreani, Annarosa; Gulamhusein, Aliya F; Eaton, John E; Schreiber, Stefan; Coltescu, Catalina.
Afiliação
  • Ji SG; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Juran BD; Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Mucha S; Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
  • Folseraas T; Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Jostins L; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Melum E; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Kumasaka N; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Atkinson EJ; Christ Church, University of Oxford, St Aldates, Oxford, UK.
  • Schlicht EM; Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Liu JZ; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Shah T; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Gutierrez-Achury J; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
  • Boberg KM; Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Bergquist A; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Vermeire S; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Eksteen B; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Durie PR; Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Farkkila M; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Müller T; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Schramm C; Department of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Sterneck M; Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
  • Weismüller TJ; Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium.
  • Gotthardt DN; Snyder Institute for Chronic Diseases, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Ellinghaus D; Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Braun F; Helsinki University and Helsinki University Hospital, Clinic of Gastroenterology, Helsinki, Finland.
  • Teufel A; Department of Internal Medicine, Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Laudes M; 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Lieb W; Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Jacobs G; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Beuers U; Integrated Research and Treatment Center-Transplantation (IFB-tx), Hannover Medical School, Hannover, Germany.
  • Weersma RK; Department of Internal Medicine 1, University Hospital of Bonn, Bonn, Germany.
  • Wijmenga C; Department of Medicine, University Hospital of Heidelberg, Heidelberg, Germany.
  • Marschall HU; Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
  • Milkiewicz P; Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Pares A; Department of Medicine I, University Medical Center, Regensburg, Germany.
  • Kontula K; Clinic of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
  • Chazouillères O; Institute of Epidemiology and Biobank PopGen, University Hospital Schleswig-Holstein, Kiel, Germany.
  • Invernizzi P; Institute of Epidemiology and Biobank PopGen, University Hospital Schleswig-Holstein, Kiel, Germany.
  • Goode E; Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
  • Spiess K; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
  • Moore C; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
  • Sambrook J; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Ouwehand WH; Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
  • Roberts DJ; Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
  • Danesh J; Department of Medicine, University of Helsinki, Helsinki, Finland.
  • Floreani A; AP-HP Hôpital Saint Antoine, Department of Hepatology, UPMC University Paris 6, Paris, France.
  • Gulamhusein AF; Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
  • Eaton JE; Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK.
  • Schreiber S; Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK.
  • Coltescu C; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Nat Genet ; 49(2): 269-273, 2017 Feb.
Article em En | MEDLINE | ID: mdl-27992413
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colangite Esclerosante / Doenças Inflamatórias Intestinais Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colangite Esclerosante / Doenças Inflamatórias Intestinais Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article