Because recent studies have implicated various nicotine receptor subunits in moderating nicotine's impact in drug-naive animals [16–18] and in humans [19,20], we decided to explore possible associations between rs16969968 and phenotypes involving reactivity to cigarettes during early smoking experimentation. We were guided by observations that individuals reporting greater positive early smoking experiences were more likely to be regular nicotine-dependent smokers [21–25]. Based on twin studies suggesting that at least 50% of the variability in smoking initiation is attributable to genetic factors [26,27], we hypothesized that some of these effects might be mediated by variations in nicotine receptor function, and in particular by the non-synonymous coding SNP rs16969968.
