A genome-wide association study of alcohol dependence

作者：Bierut Laura J^*; Agrawal Arpana; Bucholz Kathleen K; Doheny Kimberly F; Laurie Cathy; Pugh Elizabeth; Fisher Sherri; Fox Louis; Howells William; Bertelsen Sarah; Hinrichs Anthony L; Almasy Laura; Breslau Naomi; Culverhouse Robert C; Dick Danielle M; Edenberg Howard J; Foroud Tatiana; Grucza Richard A; Hatsukami Dorothy; Hesselbrock Victor; Johnson Eric O; Kramer John; Krueger Robert F; Kuperman Samuel; Lynskey Michael; Mann Karl; Neuman Rosalind J

来源：Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(11): 5082-5087.

DOI：10.1073/pnas.0911109107

• genetics
• candidate genes

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 alpha 2 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.

• 出版日期2010-3-16
• 单位上海市精神卫生中心