In summary, BOLD responses to preferred alcoholic drink odors in medial prefrontal cortical cortex differed along a gradient of “allele dose” in this GABRA2 polymorphism. Specifically, subjects who were homozygous for the A risk allele had a larger response to AO as compared to ApCO. The medial frontal regions in which this occurred (most robustly left mPFC, right vmPFC) are proximate to the right mPFC region that discriminated between a family history of alcoholism in a subsample of non-dependent heavy drinkers (Kareken et al., 2010). However, a genotype difference occurred in the opposite direction in the VTA, where AO (compared to ApCO) responses were greater in individuals with only one copy of the risk allele. This finding did not remain significant in some analytic scenarios, and the VTA region did not prove sensitive to a family history of alcoholism. These results raise the possibility that polymorphisms in the GABRA2 gene, or perhaps in adjacent genes in high linkage disequlibrium with GABRA2 (Enoch et al., 2009), may alter the mesocorticolimbic circuit's sensitivity to reward cues, particularly in medial prefrontal areas shown
