Limitations of these trials have been described previously (38), and include lack of generalizability to individuals of non-European descent, probable unmeasured genetic heterogeneity not captured by these four variants (63), modest sample size, and minor methodological differences across the two studies such as shorter duration of pharmacological and behavioral treatment, less intensive counseling and lower EOT abstinence rates in Study 2 (10 weeks) vs. Study 1 (12 weeks), as discussed in other publications (38, 64). Fewer people were genotyped for SLC6A3 in Study 1 and participants were not included in AGES unless they had at least 2/4 markers. Hence, there are fewer participants with SCL6A3 represented in AGES in comparison to those with DRD4, which could contribute to differences in EOT-PPA outcomes between the previously published papers involving the two RCTs in this report (38). In addition, because this initial 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
