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Title:	Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease
Author:	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
Notes:	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.
Subject(s):	-Malalties inflamatòries intestinals -Gastroenterologia -Inflamació -Inflammatory bowel diseases -Gastroenterology -Inflammation
Rights:	cc-by-nc-sa (c) Ji et al., 2017 http://creativecommons.org/licenses/by-nc-sa/3.0/es
Document type:	Article Article - Published version
Published by:	Nature Publishing Group
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