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 OR_G 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.