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Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Original publication

DOI

10.1073/pnas.1017288108

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

06/04/2011

Volume

108

Pages

7119 - 7124

Addresses

Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London SE5 8AF, United Kingdom. gunter.schumann@kcl.ac.uk

Keywords

Animals, Humans, Mice, Drosophila melanogaster, Proteins, Nuclear Proteins, Alcohol Drinking, Gene Expression Regulation, Genotype, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study