Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease

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 ge...

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Detalles Bibliográficos
Autores: 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, Parés Darnaculleta, Albert, Kontula, Kimmo, Chazouillères, Olivier, Invernizzi, Pietro, Goode, Elizabeth C., Spiess, Kelly, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem H., Roberts, David J., Danesh, John, Floreani, Annarosa, Gulamhusein, Aliya F., Schreiber, Stefan, Coltescu, Catalina, Bowlus, Christopher L., Luketic, Velimir A., Odin, Joseph A., Chopra, Kapil B., Kowdley, Kris V., Chalasani, Naga, Manns, Michael P., Srivastava, Brijesh, Mells, George, Sandford, Richard N., Alexander, Graeme, Gaffney, Daniel J., Chapman, Roger W., Hirschfield, Gideon M., Andrade, Mariza de, Rushbrook, Simon M., Franke, Andre, Karlsen, Tom H., Lazaridis, Konstantinos N., Anderson, Carl A., UK-PSC Consortium, International IBD Genetics Consortium, International PSC Study Group
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120628
Acceso en línea:https://hdl.handle.net/2445/120628
Access Level:acceso abierto
Palabra clave:Malalties inflamatòries intestinals
Gastroenterologia
Inflamació
Inflammatory bowel diseases
Gastroenterology
Inflammation
Descripción
Sumario: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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