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Gamma-aminobutyric acid A receptor, α-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis.

Abstract

OBJECTIVES
The available evidence from the genetic association studies (GAS) published to date on the association between variants in the GABRA2 gene and alcoholism has produced inconclusive results. To interpret these results, a meticulous meta-analysis of all available studies was carried out.
METHODS
The PubMed database and the HuGE Navigator were searched for published GAS-related variants in the GABRA2 gene with susceptibility to alcoholism. Then, the GAS were synthesized to decrease the uncertainty of estimated genetic risk effects. The risk effects were estimated on the basis of the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G)), a model-free approach. Cumulative and recursive cumulative meta-analyses (CMA) were also carried out to investigate the trend and stability of effect sizes as evidence accumulates.
RESULTS
Fourteen variants investigated in eight studies were analyzed. Significant associations were derived for four variants either for the allele contrast or for the OR(G). In particular, the variants rs279858 and rs279845 showed marginal significance for OR(G): OR(G)=1.27 (1.01-1.60) and OR(G)=1.49 (1.02-2.19), respectively. Also, the variants rs567926 and rs279844 showed significance for the allele contrast: OR=1.24 (1.06-1.46) and OR=1.23 (1.08-1.43), respectively; the ORG produced similar results. The variant rs279858 produced a large heterogeneity between studies. CMA showed a trend of an association only for the variant rs567926. Recursive CMA indicated that more evidence is needed to conclude on the status of significance of all variants.
CONCLUSION
There is evidence that variants in the GABRA2 gene are associated with alcoholism. However, the present findings should be interpreted with caution.

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  • Publisher Full Text

    • Authors

    Zintzaras E

    Institution

    Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. zintza@med.uth.gr

    Source

    Psychiatric genetics 22:4 2012 Aug pg 189-96

    MeSH

    Alcoholism
    Alleles
    Confidence Intervals
    Genetic Heterogeneity
    Genetic Predisposition to Disease
    Humans
    Odds Ratio
    Polymorphism, Single Nucleotide
    Publication Bias
    Receptors, GABA-A
    Risk Factors

    Pub Type(s)

    Journal Article
    Meta-Analysis

    Language

    eng

    PubMed ID

    22555154