This research employs the largest combined sample and the most comprehensive group of smoking cessation pharmacotherapies to be submitted to pharmacogenetic analyses. In our analyses, we have adjusted for trial randomization arm, participant demographics, nicotine dependence measures, and genetic covariates. This study refines previous pharmacogenetic smoking cessation associations at four nAChR SNPs of current interest, identifies novel associations of two nAChR loci on smoking cessation outcomes in individuals randomized to NRT, and identifies at least two mechanisms by which a nAChR SNP may influence abstinence. The significant SNP PG association results require testing in independent RCT arms to validate the specific PG associated effects. Additional testing in larger numbers of RCTs arms, and using multiple treatment meta-analysis techniques, may establish whether there are specific SNP associations with PGs not identified in this analysis.
