A genome-wide association study of alcohol dependence.

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; Nöthen, Markus M; Nurnberger, John I; Porjesz, Bernice; Ridinger, Monika; Saccone, Nancy L; Saccone, Scott F; Schuckit, Marc A; Tischfield, Jay A; Wang, Jen C; Rietschel, Marcella; Goate, Alison M; Rice, John P

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

2010-03-02

Publication Volume

107

Publication Issue

11

Publication Begin

5082

Publication End

7

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 alpha2 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.

Citation

Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nöthen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP; Gene, Environment Association Studies Consortium. A genome-wide association study of alcohol dependence. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5082-7. doi: 10.1073/pnas.0911109107. Epub 2010 Mar 2. PMID: 20202923; PMCID: PMC2841942.

DOI

10.1073/pnas.0911109107