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Edited by Mary-Claire King, University of Washington, Seattle, WA, and approved February 2, 2010 (received for review September 25, 2009)
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.
Footnotes
- 1To whom correspondence should be addressed. E-mail: bierutl{at}psychiatry.wustl.edu.
Author contributions: L.J.B., K.K.B., A.L.H., H.J.E., A.M.G., and J.P.R. designed research; L.J.B., K.K.B., K.F.D., S.F., N.B., D.H., V.H., E.O.J., J.K., S.K., K.M., M.M.N., J.I.N., B.P., M. Ridinger, J.A.T., and J.P.R. performed research; K.M. contributed new reagents/analytic tools; L.J.B., A.A., C.L., E.P., L.F., W.H., S.B., M. Rietschel, and J.P.R. analyzed data; and L.J.B., A.A., K.K.B., K.F.D., C.L., E.P., S.F., L.F., W.H., S.B., A.L.H., L.A., N.B., R.C.C., D.M.D., H.J.E., T.F., R.A.G., D.H., V.H., E.O.J., J.K., R.F.K., S.K., M.L., R.J.N., J.I.N., B.P., N.L.S., S.F.S., M.A.S., J.A.T., J.C.W., M. Rietschel, A.M.G., and J.P.R. wrote the paper.
Conflict of Interest Statement: L.J.B., J.P.R., A.M.G., S.F.S., and J.C.W. are inventors on the patent “Markers for Addiction” (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. N.L.S. is the spouse of S. F.S., who is listed as an inventor on the patent. L.J.B. served as a consultant for Pfizer Inc. in 2008.
This article is a PNAS Direct Submission.
Data deposition: Data can be obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p1.
This article contains supporting information online at www.pnas.org/cgi/content/full/0911109107/DCSupplemental.
A genome-wide association study of alcohol dependence
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