investigation aimed solely to test whether or not the AGES predicts treatment response, we did not analyze the analytic and clinical utility of particular AGES cutoffs that could be applied in clinical settings such as receiver-operator curves and/or comparisons of the predictive value of AGES to validated non-genetic predictors of smoking cessation (e.g., FTND). Another limitation is that the multilocus dopamine genetic score explains a fraction of the phenotypic variances in reward pathway responsivity and smoking cessation and there are many other genetic variants that were not included in the AGES. Several investigations have reported associations with smoking cessation with polymorphisms in cholinergic receptor (e.g., CHRNA5-A3-B4 (14, 56, 57, 65); CHRNB2 (14, 41, 57)) and other genes indirectly related to dopamine neurotransmission (e.g., GALR1 or FREQ) (66, 67) or the metabolism of bupropion (CYP2B6) (36, 37), but these polymorphisms have not – to our knowledge – been replicated in clinical trials of bupropion demonstrating gene × drug interactions. However, dopamine pathway polymorphisms have been the most widely reported pharmacological pathway influencing bupropion efficacy for smoking cessation in retrospective analyses of clinical trials (12, 13, 21). In addition, the AGES formula applied equal weights to each polymorphism as a default, counted
