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PMID: 20202923 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A genome-wide association study of alcohol dependence.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 11 ·2010-03-16 ·Pages 5082-7

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, 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

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.

MeSH Terms
Adult Alcoholism/genetics Case-Control Studies Family Female Genome-Wide Association Study Humans Male Odds Ratio Polymorphism, Single Nucleotide/genetics Receptors, GABA-A/genetics Reproducibility of Results
Chemicals
GABRA2 protein, human Receptors, GABA-A
Authors & Affiliations
40 authors, click to expand affiliations / ORCID
Bierut Laura J
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. [email protected]
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
Gene, Environment Association Studies Consortium
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0911109107
Email
[email protected]
Published
2010-03-16
Epub
2010-00-02
Pages
5082-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2841942
Subset
IM
Grants
NHGRI NIH HHS · U01HG004438 · United States
NHGRI NIH HHS · U01 HG004438 · United States
NCI NIH HHS · P01 CA089392-07 · United States
NCI NIH HHS · P01 CA089392 · United States
NHGRI NIH HHS · HHSN268200782096C · United States
NIAAA NIH HHS · K02 AA018755 · United States
NIDA NIH HHS · K02 DA021237 · United States
NIDA NIH HHS · R01 DA019963-01A2 · United States
NIAAA NIH HHS · U10 AA008401 · United States
NIDA NIH HHS · R01 DA019963-03 · United States
NHGRI NIH HHS · U01 HG004446 · United States
NHGRI NIH HHS · U01 HG004422-02 · United States
NHGRI NIH HHS · U01 HG004422 · United States
NIDA NIH HHS · R01 DA019963-02 · United States
NIDA NIH HHS · R01 DA013423-05 · United States
NIDA NIH HHS · R01 DA019963 · United States
NIDA NIH HHS · R01 DA013423 · United States
External Links
PubMed source DOI: 10.1073/pnas.0911109107 PMC Full Text View journal details
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