A genome-wide association study of alcohol dependence

TLDR

Excessive alcohol consumption is a leading cause of preventable death in the U.S., and about 14 % of users develop alcohol dependence, characterized by tolerance, withdrawal, and continued drinking despite serious problems. The study aims to further dissect the alcoholism phenotype to separate the effects of comorbid substance‑use disorders and identify genetic variants linked to alcohol dependence. The authors performed a genome‑wide association study on 1,897 European‑American and African‑American alcohol‑dependent individuals and 1,932 alcohol‑exposed nondependent controls, genotyping constitutional DNA with an Illumina 1M beadchip and independently evaluating the GABRA2 candidate gene. No SNPs reached replication significance, but five nominally significant SNPs in GABRA2 were identified with odds ratios between 1.11 and 1.16.

Abstract

Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10 −5 , but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2 , which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.