The use of a genetic efficacy score has the potential to simplify the incorporation of multiple informative polymorphisms to the process of genetically tailored treatment for smoking cessation. Here we report evidence of bupropion moderation of a smoking cessation outcome by an additive genetic efficacy score (AGES) composed of polymorphisms previously associated with smoking cessation and prior evidence of effects on gene expression and nicotine dependence endophenotypes in neuroimaging studies (See Supplemental Table S1 for details). We were interested in the effect of the AGES on days to first lapse because this phenotype (a) is predictive of longer-term abstinence outcomes (34); (b) spans the full period of exposure to drug during which gene × drug interactions are biologically plausible and more likely to be detected; (c) complies with recommendations from the Society for Research on Nicotine and Tobacco to report survival analyses as well as point-prevalence abstinence (34); (d) would be testing the proof of concept AGES using a phenotype (time to first smoking lapse) (TTFSL) not previously reported in extant publications of these four genetic variants using these two
