This study was stimulated by three previously established findings: (a) an association of GABRA2 variants with alcoholism; (b) an association of impulsive behavior with alcoholism, and (c) an emerging role of the insula in conscious urges to take drugs and maintain the addictive behavior 18. We thus sought to determine whether alcoholism-associated GABRA2 variants were also associated with impulsive behaviors and with insula activation during reward and loss anticipation. In this study, the G allele and corresponding haplotype (GG/GG) for both SNPs previously described as the high-risk haplotype by four studies5, 6, 8, 9, are associated with higher probability to have alcoholic symptoms, higher scores of the NEO-PI-R Impulsiveness facet, and with greater insula activation during anticipation of reward and loss and this activation is correlated with NEO-PI-R Impulsiveness scores. The convergence of these findings suggests that variation in GABRA2 contributes to the risk of alcoholism through the influence on impulsive behaviors and supports previous studies that relate GABRA2 with impulsive-related traits such as conduct disorder 48 and this effect may take place at least in part in the insula.
