The strengths of the present investigation include its relevance to clinical translation towards personalized medicine for smoking cessation, the use of an a priori formula based on biological knowledge, rigorous placebo-controlled design and application of a refined cessation phenotype (i.e., days to lapse) that may be more sensitive for detecting treatment effects than composite phenotypes (e.g., point-prevalence abstinence) (59, 62). Moreover, these results add to an emerging literature utilizing formulas designed to aggregate variation in multiple dopamine polymorphisms on various phenotypes (23, 26, 27). Notably, McGeary et al. investigated an AGES that included several of the variants studied here in a placebo-controlled bupropion smoking cessation trial in 90 alcoholics and found no main effects or moderation of treatment efficacy on relapse risk (23). The current sample was larger and afforded more statistical power to highlight the potential utility of AGES in the general population of treatment-seeking smokers.
