Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

TitleGenome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
Publication TypeJournal Article
Year of Publication2011
AuthorsSchumann, G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D, Desrivières S, Aliev FA, Khan AA, Amin N et al.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue17
Pagination7119-24
Date Published2011 Apr 26
ISSN1091-6490
KeywordsAlcohol Drinking, Animals, Drosophila melanogaster, European Continental Ancestry Group, Female, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Male, Mice, Nuclear Proteins, Polymorphism, Single Nucleotide, Proteins, Quantitative Trait, Heritable
Abstract

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.

DOI10.1042/AN20110027
Alternate JournalProc. Natl. Acad. Sci. U.S.A.