The only other neuroimaging study we are aware of investigating CHRNA5-A3-B4, studied resting-state functional connectivity (i.e., the synchronization of intrinsic low-frequency fluctuations between brain regions outside of task performance) within the corticostriatal circuit. Similar to smokers [98], rs16969968 risk allele carriers had reduced functional coupling of the dorsal anterior cingulate cortex (dACC) and striatum/extended amygdala, regardless of smoking status [99]. This study also found that CHRNA3 rs578776 G (risk) allele carriers had elevated dACC and thalamic resting state connectivity, which was correlated with smoking just prior to the imaging session (measured via expired CO levels). Given these differential associations with lifetime and immediate smoking, and the extant literature demonstrating the independence of their effects, the authors posit that rs16969968 and rs578776 genotypes contribute to trait and state aspects of smoking respectively [99]. In contrast to the study by Janes and colleagues [100], the results of this study suggest that CHRNA5-A3-B4 genetic risk covaries with corticostriatal correlates of smoking.
