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

Buch S, Stickel F, Trepo E, Way M, Herrmann A, Nischalke HD, Brosch M, Rosendahl J, Berg T, Ridinger M, Rietschel M, Mcquillin A, Frank J, Kiefer F, Schreiber S, Lieb W, Soyka M, Semmo N, Aigner E, Datz C, Schmelz R, Brueckner S, Zeissig S, Stephan AM, Wodarz N, Deviere J, Clumeck N, Sarrazin C, Lammert F, Gustot T, Deltenre P, Voelzke H, Lerch MM, Mayerle J, Eyer F, Schafmayer C, Cichon S, Noethen MM, Nothnagel M, Ellinghaus D, Huse K, Franke A, Zopf S, Hellerbrand C, Moreno C, Franchimont D, Morgan MY, Hampe J (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Nature Genetics Nature Publishing Group

Book Volume: 47

Pages Range: 1443-8

Journal Issue: 12

DOI: 10.1038/ng.3417

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.

Authors with CRIS profile

Steffen Zopf Medizinische Fakultät

Additional Organisation(s)

Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

University College London (UCL) GB United Kingdom (GB) Technische Universität Dresden DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Universität Regensburg DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Inselspital, Universitätsspital Bern CH Switzerland (CH) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Université libre de Bruxelles (ULB) / Free University of Brussels BE Belgium (BE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Universitätsspital Basel CH Switzerland (CH) Universität zu Köln DE Germany (DE) Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut (FLI) DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universitätsspital Zürich (USZ) CH Switzerland (CH)

How to cite

APA:

Buch, S., Stickel, F., Trepo, E., Way, M., Herrmann, A., Nischalke, H.D.,... Hampe, J. (2015). A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nature Genetics, 47(12), 1443-8. https://doi.org/10.1038/ng.3417

MLA:

Buch, Stephan, et al. "A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis." Nature Genetics 47.12 (2015): 1443-8.

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