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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

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Authors
Liu, Jimmy Z
Hov, Johannes Roksund
Folseraas, Trine
Ellinghaus, Eva
Rushbrook, Simon M
Doncheva, Nadezhda T
Andreassen, Ole A
Weersma, Rinse K
Weismüller, Tobias J
Eksteen, Bertus
Invernizzi, Pietro
Hirschfield, Gideon M
Gotthardt, Daniel Nils
Pares, Albert
Ellinghaus, David
Shah, Tejas
Juran, Brian D
Milkiewicz, Piotr
Rust, Christian
Schramm, Christoph
Müller, Tobias
Srivastava, Brijesh
Dalekos, Georgios
Nöthen, Markus M
Herms, Stefan
Winkelmann, Juliane
Mitrovic, Mitja
Braun, Felix
Ponsioen, Cyriel Y
Croucher, Peter J P
Sterneck, Martina
Teufel, Andreas
Mason, Andrew L
Saarela, Janna
Leppa, Virpi
Dorfman, Ruslan
Alvaro, Domenico
Floreani, Annarosa
Onengut-Gumuscu, Suna
Rich, Stephen S
Thompson, Wesley K
Schork, Andrew J
Næss, Sigrid
Thomsen, Ingo
Mayr, Gabriele
König, Inke R
Hveem, Kristian
Cleynen, Isabelle
Gutierrez-Achury, Javier
Ricaño-Ponce, Isis
van Heel, David
Björnsson, Einar
Sandford, Richard N
Durie, Peter R
Melum, Espen
Vatn, Morten H
Silverberg, Mark S
Duerr, Richard H
Padyukov, Leonid
Brand, Stephan
Sans, Miquel
Annese, Vito
Achkar, Jean-Paul
Boberg, Kirsten Muri
Marschall, Hanns-Ulrich
Chazouillères, Olivier
Bowlus, Christopher L
Wijmenga, Cisca
Schrumpf, Erik
Vermeire, Severine
Albrecht, Mario
Rioux, John D
Alexander, Graeme
Bergquist, Annika
Cho, Judy
Schreiber, Stefan
Manns, Michael P
Färkkilä, Martti
Dale, Anders M
Chapman, Roger W
Lazaridis, Konstantinos N
Franke, Andre
Anderson, Carl A
Karlsen, Tom H
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Issue Date
2013-06

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Citation
Nat. Genet. 2013, 45 (6):670-5
Abstract
Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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To access publisher's full text version of this article click on the hyperlink at the bottom of the page
Additional Links
http://dx.doi.org/10.1038/ng.2616
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667736/
Rights
restrictedAccess
ae974a485f413a2113503eed53cd6c53
10.1038/ng.2616
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