Journal
NATURE GENETICS
Volume 47, Issue 12, Pages 1443-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.3417
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Funding
- German Ministry of Education and Research through the Virtual Liver Network
- PopGen 2.0 network biobank [01EY1103]
- medical faculties of TU Dresden and Christian Albrechts University Kiel
- Swiss National Funds [310030_138747]
- Federal Ministry of Education and Research
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Federal Ministry of Education and Research [BMBF GANI-MED 03152061A, BMBF 0314107]
- European Union
- EFRE-State Ministry of Economics [V-630-S-150-2012/132/133]
- German Federal Ministry of Education and Research (BMBF) through the Integrated Networks IntegraMent and Sysmed Alcohol [01ZX1314A, 01ZX1311A]
- DFG (Deutsche Forschungsgemeinschaft)-funded Excellence Cluster ImmunoSensation
- Deutsche Krebshilfe [107865]
- German Federal Ministry of Education and Research (BMBF) within the framework of the e: Med research and funding concept [01ZX1306A]
- DFG Excellence Cluster, 'Inflammation at Interfaces' [306]
- Foundation for Experimental Medicine (Zurich, Switzerland)
- University College London
- Avon and Wiltshire Mental Health Partnership
- Lincolnshire Partnership
- Belgian Medical Genomics Initiative (BeMGI) - phase VII Interuniversity Attraction Poles (IAP) program of the Belgian Federal Science Policy Office (BELSPO)
- Fund for Scientific Research-FNRS (F.R.S.-FNRS)
- Swiss National Science Foundation (SNF) [310030_138747] Funding Source: Swiss National Science Foundation (SNF)
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Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world(1-3). 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 x 10(-9)) and TM6SF2 (P = 7.89 x 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 x 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.
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