Most prior studies of the relation between GAD genes and substance addictive behaviors have used animal models. Mice and rat studies have shown that GAD genes expression was altered during diazepam withdrawal (Izzo et al., 2001), alcohol withdrawal or dependence (Eravci et al., 2000), or chronic exposure to high-dose methamphetamine (Zhang et al., 2006). However, the evidence of expression alteration of GAD genes is not consistent (Fehr et al., 2003), and gene expression levels appear to vary by brain region in response to drug treatment. We are aware of only two published reports examining the association of GAD genes with alcohol-related phenotypes in humans. Loh et al. (2006) examined the association of 9 SNPs for GAD1 and 3 SNPs for GAD2 in 140 alcoholic cases and 146 controls in Han Taiwanese men. They found evidence of association with AD in GAD1 but not GAD2. Lappalainen et al. (2007) genotyped 13 SNPs for GAD2 in a sample of 113 Russian males with AD and 100 controls and found modest association for a functional marker, rs2236418 (−243 A > G). However, in
