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

Publication

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

Journal Paper/Review - Apr 21, 2013

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

Citation

Thomsen I, Vatn M, Silverberg M, Duerr R, Padyukov L, Brand S, Sans M, Annese V, Achkar J, Melum E, Durie P, Sandford R, Mayr G, König I, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Boberg K, Marschall H, Schreiber S, Manns M, Färkkilä M, Dale A, Chapman R, Lazaridis K, Franke A, Anderson C, Cho J, Bergquist A, Alexander G, Chazouillères O, Bowlus C, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M, Rioux J, Karlsen T, Næss S, Liu J, Gotthardt D, Pares A, Ellinghaus D, Shah T, Juran B, Milkiewicz P, Rust C, Schramm C, Hirschfield G, Invernizzi P, Eksteen B, Hov J, Folseraas T, Ellinghaus E, Rushbrook S, Doncheva N, Andreassen O, Weersma R, Weismüller T, Müller T, Srivastava B, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich S, Thompson W, Mason A, Teufel A, Sterneck M, Dalekos G, Nöthen M, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen C, Croucher P, Schork A. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nat Genet 2013; 45:670-5.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2013; 45

Publication Date

Apr 21, 2013

Issn Electronic

1546-1718

Pages

670-5

Brief description/objective

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.