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


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.

SUBMITTER: Liu JZ 

PROVIDER: S-EPMC3667736 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20130421 6


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. Desp  ...[more]

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