the minor allele is associated with reduced abstinence in the PLA PG at EOT and at 6MO, and with increased abstinence in the NRT PG at 6MO. The directionality of the effect on abstinence in individuals prescribed PLA is expected, as previously shown for one trial included in this analysis [52], but the directionality with the NRT PG is unexpected, given the prior associations of rs1051730 with nicotine dependence [23], with reduced abstinence at four weeks in multiple RCTs that randomize participants to NRT [50], and considering the inverse associations of nicotine dependence and abstinence [5,6]. We adjusted for the nicotine dependence measures CPD and FTND in our models because we previously observed significant inverse associations of these measures with abstinence in the eight RCTs (data not shown), concordant with a published meta-analysis [6]. Association analyses of chr15q25.1 SNPs and abstinence relations that exclude nicotine dependence measures modestly reduced rs1051730 SNP effects, suggesting that the influences of rs1051730 and nicotine dependence on abstinence are related. Mediation analysis examined the relations of rs1051730 with abstinence in the PLA and NRT PGs at 6MO, and the extent to which this relation was mediated by nicotine dependence measures; we observed significant mediation effects
