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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-06

AUTHORS

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

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. More... »

PAGES

670-675

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    6

    VOLUME

    45

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2616

    DOI

    http://dx.doi.org/10.1038/ng.2616

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045221990

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23603763


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