A genome-wide association study of alcohol dependence

• DOI: 10.1073/pnas.0911109107
• Publication Date: 2010-03-03T02:12:16Z
• Authors: Laura J. Bierut; Arpana Agrawal; Kathleen K. Bucholz; Kimberly F. Doheny; Cathy Laurie; Elizabeth Pugh; Sherri Fisher; Louis Fox; William Howells; Sarah Bertelsen; Anthony L. Hinrichs; Laura Almasy; Naomi Breslau; Robert C. Culverh...; Danielle M. Dick; Howard J. Edenberg; Tatiana Foroud; Richard A. Grucza; Dorothy Hatsukami; Victor Hesselbrock; Eric O. Johnson; John Kramer; Robert F. Krueger; Samuel Kuperman; Michael Lynskey; Karl Mann; Rosalind J. Neuman; Markus M. Nöthen; John I. Nurnberger; Bernice Porjesz; Monika Ridinger; Nancy L. Saccone; Scott F. Saccone; Marc A. Schuckit; Jay A. Tischfield; Jen C. Wang; Marcella Rietschel; Alison M. Goate; John P. Rice
• Keywords: Adult; Male; GABA-A; 610; Reproducibility of Results; Single Nucleotide; Receptors, GABA-A; Polymorphism, Single Nucleotide; 3. Good health; Alcoholism; 03 medical and health sciences; 0302 clinical medicine; Case-Control Studies; Receptors; Odds Ratio; Humans; Family; Female; Polymorphism; Genome-Wide Association Study

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.