Title
Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
Document Type
Article
Publication Date
2-1-2017
Publication Title
Nature genetics
Keywords
Adaptor Proteins, Signal Transducing; Alleles; Cholangitis, Sclerosing; Colitis, Ulcerative; Genome-Wide Association Study; Humans; Inflammatory Bowel Diseases; Polymorphism, Single Nucleotide; RNA, Messenger; Risk Factors
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 (r
Clinical Institute
Digestive Health
Department
Gastroenterology
Recommended Citation
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; and Anderson, Carl A, "Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease." (2017). Articles, Abstracts, and Reports. 2433.
https://digitalcommons.providence.org/publications/2433
