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

Journal article

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.

Authors: Schumann, G; Coin, L; Lourdusamy, A; Charoen, P; Berger, K

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 108
• Issue: 17
• Pages: 7119-7124
• Publication date: 2011-04-06
• DOI: 10.1073/pnas.1017288108
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Quantitative Trait, Heritable; Female; Drosophila melanogaster; Animals; Alcohol Drinking; Gene Expression Regulation; Humans; Mice; Male; Genotype; Genome-Wide Association Study; European Continental Ancestry Group; Proteins; Nuclear Proteins; Polymorphism, Single Nucleotide