Genetics plays a role in smokers’ cessation attempts (heritabilities of ~50 % [28, 29]), and response to cessation treatments [30]. Pharmacogenetic analyses of smoking cessation clinical trials suggest that prospective abstinence is affected by loci influencing reward system responses to nicotine and pharmacotherapeutics, nicotine and bupropion metabolism, and varenicline clearance [30]. Analyses of chr15q25.1 SNPs and prospective abstinence by pharmacotherapy have been mixed: null [31–33], reduced in participants randomized to placebo [34], and increased in participants randomized to multiple therapies [35, 36]. In the largest analysis to date [37], chr15q25.1 smoking-heaviness risk SNPs were found to be associated with reduced abstinence in participants randomized to placebo, and increased abstinence in participants randomized to nicotine replacement therapy (NRT). In contrast, studies on functional variation in the nicotine metabolizing enzyme cytochrome P450 oxidase 2A6 (CYP2A6) [38, 39] translate robustly to smoking behaviors [40, 41] and prospective abstinence, using either nicotine metabolite [42–45], or genetic [46–48] analyses. In brief, recent findings suggest that slow nicotine metabolizers are less nicotine dependent and have similar quit rates across therapies, while fast nicotine metabolizers are more nicotine dependent and may benefit from combined treatments with NRT, bupropion, or varenicline.
