the African American STOMP meta-analysis, while a correlated SNP (rs1051730 A allele) accounted for 0.5% of the phenotypic variance in smoking quantity in populations of European ancestry.18 Evidence from animal and magnetic resonance imaging studies support these findings; a study of CHRNA5 knockout mice showed that re-expressing this gene in the medial habenula, which extends projections to a brain region shown to mediate nicotine withdrawal, abolished the inhibitory effects of nicotine while maintaining the reinforcing effects of nicotine.49, 50 In a functional magnetic resonance imaging study of smokers, genetic variation in CHRNA5 appeared to also affect the reactivity to smoking cues in the insula, hippocampus and dorsal striatum, regions implicated in addictive behavior and memory.51 Thus, it is biologically plausible that increased expression of CHRNA5 could be associated with smoking quantity as a consequence of neuro-adaptations resulting from complex interactions between genes and environment.
