Numerous studies have reported moderation of bupropion efficacy for smoking cessation by single genetic polymorphisms (21). The limitation of this approach include a lack of statistical power to detect effects of single variants, genetic confounders and non-genetic confounders (22). The use of an additive genetic scale has the advantages of considering the collective impact of several variants, relying on prior knowledge of alleles (in contrast to agnostic genome-wide association [GWAS] approaches) and provides greater statistical power than modeling each variant individually if the assumptions of the additive genetic scale accurately model the biological pathway under study. McGeary and colleagues (23) reported the use of a proof-of-concept, bupropion-specific dopamine pathway additive genetic risk score that was associated with smoking cessation in a previous clinical trial of abstinent, alcoholic smokers (23), that assumes an additive genetic model of four dopamine-based risk alleles using the following criteria for marker selection: (i) evidence of moderation of drug response in at least two separate clinical trials; (ii) evidence of functional impact of variant on gene expression and/or endophenotypes of nicotine dependence in humans; and (iii)
