Three particularly promising candidate genes, GABRA4, GABRB1 and CLOCK, are located within or very close to the autosome-wide significant linkage region on chromosome 4. The two GABA receptor-encoding genes, GABRA4 and GABRB1, are located ~5 Mb upstream of the 1-lod support interval, and are part of a gene cluster encoding alpha 4, alpha 2 and gamma 1 subunits of the gamma-aminobutyric acid (GABA) alpha receptors, which are ligand-gated chloride channels that mediate inhibition in synaptic signal transduction in the mammalian central nervous system. Functional evidence shows that α4-containing GABAA receptors in the nucleus accumbens mediate alcohol intake [Rewal et al., 2009].
