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The Role of GABRA2 on risk for Alcohol, Nicotine and Cannabis Dependence in the Iowa Adoption Studies
Journal article   Peer reviewed

The Role of GABRA2 on risk for Alcohol, Nicotine and Cannabis Dependence in the Iowa Adoption Studies

Robert A Philibert, Tracy D Gunter, Steven R. H Beach, Gene H Brody, Nancy Hollenbeck, Allan Andersen and William Adams
Psychiatric genetics, Vol.19(2), pp.91-98
04/2009
DOI: 10.1097/YPG.0b013e3283208026
PMCID: PMC3643116
PMID: 19672139

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Abstract

A number of studies have demonstrated that genetic variation at GABRA2 alters vulnerability to alcohol dependence. However, the exact identity of the causal variant(s), the relationship of these variants to other forms of substance use and behavioral illness is uncertain. Therefore, we genotyped 516 subjects from the Iowa Adoption Studies, a large longitudinal case and control adoption study of substance use, at 39 single nucleotide polymorphisms encompassing the GABRA2 locus and analyzed them with respect to their lifetime history of three common forms of substance use (alcohol (AD), nicotine (ND) and cannabis dependence (CD)), major depressive disorder (MDD) and antisocial personality disorder (ASPD) and relevant exposure variables. Using regression analysis, we found substantial evidence that both GABRA2 genotype and haplotype are significantly related to vulnerability to AD, ND and CD with the strongest relationships noted with respect to ND. Consistent with prior studies suggesting exposure is an important step in the development of substance use, we found the inclusion of substance exposure data in to our analytic models markedly increased the strength of the genetic associations of GABRA2 haplotype with substance use. Finally, we report that the genetic effects were markedly more pronounced in females than in males. We conclude that genetic variation at or near the GABRA2 locus significantly effects vulnerability not only to AD, but to other forms of substance use including ND and CD, and that the effects may be sex dependent.

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