Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
18727688
TITLE
The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Multiple studies have shown that genetic variation in the alpha-2 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population.
METHODS NlmCategory: METHODS
We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use.
RESULTS NlmCategory: RESULTS
We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use.
CONCLUSIONS NlmCategory: CONCLUSIONS
The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.
DATE PUBLISHED
2008 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/08/22
pubmed 2008/08/30 09:00
medline 2008/12/17 09:00
entrez 2008/08/30 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lind PA Lind Penelope A PA Genetic Epidemiology, Queensland Institute of Medical Research, Royal BrisbaneHospital, Brisbane, Queensland, Australia. penelope.lind@qimr.edu.au
Macgregor S Macgregor Stuart S
Agrawal A Agrawal Arpana A
Montgomery GW Montgomery Grant W GW
Heath AC Heath Andrew C AC
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 32
ISSUE: 10
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2008
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1530-0277
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA007728 NIAAA NIH HHS United States
AA013321 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA007535-05S1 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013321-04 NIAAA NIH HHS United States
R01 AA013326-04 NIAAA NIH HHS United States
R01 AA014041-04 NIAAA NIH HHS United States
R37 AA007728 NIAAA NIH HHS United States
R37 AA007728-19 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Alcoholism genetics
Australia genetics
European Continental Ancestry Group genetics
Female genetics
Haplotypes genetics
Humans genetics
Male genetics
Marijuana Abuse genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Receptors, GABA-A genetics
Smoking genetics
Survival Analysis genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 GABRA2 protein, human
0 Receptors, GABA-A
OTHER ID's
OTHERID SOURCE
NIHMS58631 NLM
PMC2575093 NLM