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

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Stephan Buch - , Department of internal Medicine I (Author)
  • Felix Stickel - , University of Zurich (Author)
  • Eric Trépo - , Université libre de Bruxelles (ULB) (Author)
  • Michael Way - , University College London (Author)
  • Alexander Herrmann - , Department of internal Medicine I (Author)
  • Hans Dieter Nischalke - , University of Bonn (Author)
  • Mario Brosch - , Department of internal Medicine I (Author)
  • Jonas Rosendahl - , Leipzig University (Author)
  • Thomas Berg - , Leipzig University (Author)
  • Monika Ridinger - , University of Regensburg, Psychiatrische Dienste Aargau (Author)
  • Marcella Rietschel - , Heidelberg University  (Author)
  • Andrew McQuillin - , University College London (Author)
  • Josef Frank - , Heidelberg University  (Author)
  • Falk Kiefer - , Heidelberg University  (Author)
  • Stefan Schreiber - , Kiel University (Author)
  • Wolfgang Lieb - , Kiel University (Author)
  • Michael Soyka - , Ludwig Maximilian University of Munich (Author)
  • Nasser Semmo - , University of Bern (Author)
  • Elmar Aigner - , University of Salzburg (Author)
  • Christian Datz - , University of Salzburg (Author)
  • Renate Schmelz - , Department of internal Medicine I (Author)
  • Stefan Brückner - , Department of internal Medicine I (Author)
  • Sebastian Zeissig - , Chair of Mucosal Immunology (Author)
  • Anna Magdalena Stephan - , TUD Dresden University of Technology (Author)
  • Norbert Wodarz - , University of Regensburg (Author)
  • Jacques Devière - , Université libre de Bruxelles (ULB) (Author)
  • Nicolas Clumeck - , Université libre de Bruxelles (ULB) (Author)
  • Christoph Sarrazin - , University Hospital Frankfurt (Author)
  • Frank Lammert - , Saarland University (Author)
  • Thierry Gustot - , Université libre de Bruxelles (ULB) (Author)
  • Pierre Deltenre - , Université libre de Bruxelles (ULB), Hôpital de Jolimont, University of Lausanne (Author)
  • Henry Völzke - , University of Greifswald (Author)
  • Markus M. Lerch - , University of Greifswald (Author)
  • Julia Mayerle - , University of Greifswald (Author)
  • Florian Eyer - , Technical University of Munich (Author)
  • Clemens Schafmayer - , Kiel University (Author)
  • Sven Cichon - , University of Basel (Author)
  • Markus M. Nöthen - , University of Bonn (Author)
  • Michael Nothnagel - , University of Cologne (Author)
  • David Ellinghaus - , Kiel University (Author)
  • Klaus Huse - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Andre Franke - , Kiel University (Author)
  • Steffen Zopf - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Claus Hellerbrand - , University of Regensburg (Author)
  • Christophe Moreno - , Université libre de Bruxelles (ULB) (Author)
  • Denis Franchimont - , Université libre de Bruxelles (ULB) (Author)
  • Marsha Y. Morgan - , University College London (Author)
  • Jochen Hampe - , Department of internal Medicine I (Author)

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.

Details

Original languageEnglish
Pages (from-to)1443-1448
Number of pages6
JournalNature genetics
Volume47
Issue number12
Publication statusPublished - 1 Dec 2015
Peer-reviewedYes

External IDs

PubMed 26482880
ORCID /0000-0003-2928-015X/work/146166311

Keywords

ASJC Scopus subject areas