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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 ; 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. ; de Andrade, Mariza ; Rushbrook, Simon M. ; Franke, Andre ; Karlsen, Tom H. ; Lazaridis, Konstantinos N. ; Anderson, Carl A.



Abstract

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; similar to 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 ...

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