The most significant association for alcohol craving in this GWAS was an intronic SNP, rs2454908, in the integrin, alpha D (ITGAD) gene which belongs to the CD11 antigen-like family of genes. To the best of our knowledge, the only potentially functionally relevant SNP that is in moderate linkage disequilibrium with this marker is in the 3′ untranslated regulatory region of the neighboring Integrin, alpha X (ITGAX) gene. How this SNP relates to alcohol craving is unknown. A number of SNPs in the potassium voltage-gated channel, KQT-like subfamily, member 3 (KCNQ3) gene were also associated with craving. The protein encoded by this gene, along with the protein product of KCNQ2 and KCNQ5, form potassium M channels that are critical in neuronal excitability and variants in KCNQ5 were previously identified in an African-American subset of individuals with alcohol dependence (Kendler et al., 2011). Of particular relevance to our study, Koyama et al (Koyama, Brodie, & Appel, 2007) have reported that ethanol induced excitation of dopamine neurons in the Ventral Tegmental Area (VTA) can be attributed to inhibition of currents in M-channels.
