A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis

Stephan Buch, Felix Stickel, Eric Trépo, Michael Way, Alexander Herrmann, Hans Dieter Nischalke, Mario Brosch, Jonas Rosendahl, Thomas Berg, Monika Ridinger, Marcella Rietschel, Andrew McQuillin, Josef Frank, Falk Kiefer, Stefan Schreiber, Wolfgang Lieb, Michael Soyka, Nasser Semmo, Elmar Aigner, Christian DatzRenate Schmelz, Stefan Brückner, Sebastian Zeissig, Anna Magdalena Stephan, Norbert Wodarz, Jacques Devière, Nicolas Clumeck, Christoph Sarrazin, Frank Lammert, Thierry Gustot, Pierre Deltenre, Henry Völzke, Markus M. Lerch, Julia Mayerle, Florian Eyer, Clemens Schafmayer, Sven Cichon, Markus M. Nöthen, Michael Nothnagel, David Ellinghaus, Klaus Huse, Andre Franke, Steffen Zopf, Claus Hellerbrand, Christophe Moreno, Denis Franchimont, Marsha Y. Morgan, Jochen Hampe

Research output: Contribution to journalArticlepeer-review

414 Scopus citations

Abstract

Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10-9) and TM6SF2 (P = 7.89 × 10-10) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10-48) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

Original languageEnglish
Pages (from-to)1443-1448
Number of pages6
JournalNature Genetics
Volume47
Issue number12
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

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