Skip to main content
eScholarship
Open Access Publications from the University of California
Refine Search

UC Davis

UC Davis Previously Published Works bannerUC Davis

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

https://doi.org/10.1038/ng.3745
Abstract

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View


Top