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 x 10-8to P = 4 x 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. Downregulation 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.

Additional Metadata
Keywords Epidemiologic, Genome-wide analysis, Transcriptional expression analysis
Persistent URL dx.doi.org/10.1073/pnas.1017288108, hdl.handle.net/1765/33466
Journal Proceedings of the National Academy of Sciences of the United States of America
Note Free full text at PubMed
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/201413 - European Network for Genetic and Genomic Epidemiology (ENGAGE), This work was funded by the European Commission 7th Framework Programme; grant id fp7/242257 - Genomic variations underlying common behavior diseases and cognition trait in human populations (ADAMS)
Citation
Schumann, G, Coin, L, Lourdusamy, A, Charoen, P, Berger, K.H, Stacey, D, … Bakker, S.J.L. (2011). Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7119–7124. doi:10.1073/pnas.1017288108