; 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. | Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Nature Genetics | ||||
| Publisher: | Nature | ||||
| Place of Publication: | NEW YORK | ||||
| Volume: | 49 | ||||
| Number of Issue or Book Chapter: | 2 | ||||
| Page Range: | pp. 269-273 | ||||
| Date: | 2017 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin I | ||||
| Identification Number: |
| ||||
| Keywords: | SUSCEPTIBILITY LOCI; PSORIATIC-ARTHRITIS; ULCERATIVE-COLITIS; TRANSCRIPTOME; METAANALYSIS; VARIANTS; REVEALS; REGIONS; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 38779 |
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 ...

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 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(G)) between PSC and ulcerative colitis (UC) (r(G) = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (r(G) = 0.04) (P = 2.55 x 10(-15)). UC and CD were genetically more similar to each other (r(G) = 0.56) than either was to PSC (P < 1.0 x 10(-15)). Our study represents a substantial advance in understanding of the genetics of PSC.
Metadata last modified: 17 Dec 2020 09:43
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