A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.
Stephan BuchFelix StickelEric TrepoMichael WayAlexander HerrmannHans Dieter NischalkeMario BroschJonas RosendahlThomas BergMonika RidingerMarcella RietschelAndrew McQuillinJosef FrankFalk KieferStefan SchreiberWolfgang LiebMichael SoykaNasser SemmoElmar AignerChristian DatzRenate SchmelzStefan BrücknerSebastian ZeissigAnna-Magdalena StephanNorbert WodarzJacques DevièreNicolas ClumeckChristoph SarrazinFrank LammertThierry GustotPierre DeltenreHenry VölzkeMarkus M LerchJulia MayerleFlorian EyerClemens SchafmayerSven CichonMarkus M NöthenMichael NothnagelDavid EllinghausKlaus HuseAndre FrankeSteffen ZopfClaus HellerbrandChristophe MorenoDenis FranchimontMarsha Y MorganJochen HampePublished in: Nature genetics (2015)
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.