Genome-wide investigations suggest that hundreds of polymorphisms moderate the efficacy of bupropion and nicotine replacement therapy (NRT) for smoking cessation, yet the variation in drug response explained by any particular allele is minor (28, 29). We are aware of only one other additive genetic predictive test for smoking cessation (30, 31) that used nominal associations from GWAS investigations of clinical trials (32, 33). The present investigation applies an alternative, pharmacological candidate gene approach by developing a predictive efficacy score for drug response to bupropion based on a priori hypotheses regarding the contributions of specific variants in both the pharmacodynamic pathway of nicotine and the dopamine pathways associated with both smoking cessation and bupropion effects. Supplemental Table S1 provides descriptions and rationale for selection of each polymorphism included in the bupropion AGES for smoking cessation.
