Allelic and haplotypic association of <i>GABRA2</i> with alcohol dependence

AbstractAlcohol dependence is a highly prevalent disorder that is associated with serious morbidity and mortality. Because the GABAA neurotransmitter receptor is an important mediator for several behavioral effects of alcohol, genes encoding GABA‐related proteins are functional candidates to influence risk of alcohol dependence. Two genome‐wide scans showed linkage of alcohol dependence to a region on chromosome 4p, which contains a cluster of genes encoding GABAA receptor subunits. A recent effort to fine map that region showed a haplotypic association of alcohol dependence to the gene encoding the GABAA receptor α‐2 subunit (GABRA2). We examined 10 single nucleotide polymorphisms (SNPs) spanning the coding region of this gene in samples of European American subjects with alcohol dependence (n = 446), and controls (n = 334) screened to exclude substance use disorders. There was evidence of association to alcohol dependence for seven adjacent markers spanning 98,000 bp in the middle and 3′‐portion of the GABRA2 gene (range of P‐values = 0.008–0.03). When the subset of the alcohol‐dependent subjects excluding those with a diagnosis of cocaine or opioid dependence or major depressive