Results revealed evidence for association between AOS and three of the five target SNPs. Importantly, AOS shows no association with rs16969968, which is strongly and reproducibly associated with nicotine dependence, smoking quantity, and cotinine levels [Furberg et al., 2010; Greenbaum and Lerer 2009; Keskitalo et al., 2009; Saccone et al., 2010b; Saccone et al., 2007; Thorgeirsson et al., 2010]. This is consistent with previous reports [Broms et al., 2012; Ducci et al., 2011; Furberg et al., 2010; Thorgeirsson et al., 2010; Weiss et al., 2008]. One explanation put forward for the lack of findings with tobacco initiation and rs16969968 is a report by Hong et al where the “risk” allele (A) predicts a defect in a dorsal anterior cingulate-ventral striatum/extended amygdala circuit whose weakness predicts addiction severity [Hong et al., 2011]. One could also reason that rs16969968 is not associated with initiation and instead more strongly related to craving and ability to quit due to the action of CHRNA5 to alter output of deep cortical layers [Picciotto and Kenny, 2012].
