One of the most successful examples of the POSITIONAL CANDIDATE GENE APPROACH in addiction research has been the identification of GABRA2 as a susceptibility factor for alcoholism. Early linkage studies in Southwest American Indians13 implicated chromosome 4p near the GABRA2/B1 cluster; these results were confirmed in some Caucasian studies,22 and became particularly convincing when linkage of alcohol-related phenotypes was combined with QUANTITATIVE TRAIT LOCUS (QTL) MAPPING of electroencephalographic quantitative trait data.23 Initial association findings of GABRA224 in that linkage region were replicated in multiple studies,25–27 so that GABRA2 is now considered a confirmed risk locus for AD.
