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Open Access Publications from the University of California

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

  • Author(s): 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
  • UK-PSC Consortium
  • International IBD Genetics Consortium
  • International PSC Study Group
  • Rushbrook, Simon M
  • Franke, Andre
  • Karlsen, Tom H
  • Lazaridis, Konstantinos N
  • Anderson, Carl A
  • et al.

Published Web Location

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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