Other candidate gene hypotheses have generally related to genes that influence neurotransmission. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in brain; alcohol exerts some of its effects via interaction with GABAA receptors. Allelic variants at loci participating in GABAergic neurotransmission have been convincingly associated with AD and related phenotypes. Porjesz et al. (2002) demonstrated, first, linkage of EEG β frequency (a quantitative trait) to chromosome 4p; then, LD to a GABAA receptor cluster, in a sample ascertained through pedigrees with multiple alcohol-dependent members. Fine mapping of this region showed allelic and haplotypic association to GABRA2 (Edenberg et al. 2004). We (Covault et al. 2004; Lappalainen et al. 2005), and others (Fehr et al. 2006) using case-control samples, replicated this major finding, with evidence of association of AD in three different populations. Enoch et al. (2006) and Soyka et al. (2008) replicated association to GABRA2, but their findings differed in the nature of the association and the specific variants that were associated with AD, respectively. There have also been non-replications of the association (Drgon et al. 2006; Matthews et al.
