Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 11, Pages 5082-5087Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911109107
Keywords
genetics; candidate genes
Categories
Funding
- National Institutes of Health (NIH) Genes
- Environment and Health Initiative (GEI) [U01 HG004422]
- GENEVA Coordinating Center [U01 HG004446]
- COGA [U10 AA008401]
- COGEND [P01 CA089392]
- FSCD [R01 DA013423]
- NIH [U01HG004438, HHSN268200782096C]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- National Genome Research Network (NGFNplus)
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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.
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