2011/04/06 by Günter Schumann, Lachlan Coin, Anbarasu Lourdusamy +97 · 1 citation
Neuroscience · Biochemistry, Genetics and Molecular Biology · #Autism Spectrum Disorder Research #Genetic Mapping and Diversity in Plants and Animals #Genetic Associations and Epidemiology
paper · doi:10.1073/pnas.1017288108
openalex publication_date 2011/04/06 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/05
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.