The results of this study should be interpreted in the context of several limitations. First, there was relatively little power to compare the magnitude of the targeted genetic effects among different active treatment conditions. The genetic risk for cessation was similar across the different pharmacotherapy conditions, indicating that multiple cessation interventions have the potential to be effective with such high-risk individuals. It is unclear if pharmacotherapy mitigates particular biological processes that lead to cessation failure, or if the genetic effect is more likely expressed at high overall levels of quitting difficulty. Second, the placebo group in the cessation trial is fairly small, which adds to the importance of future replication. However, reported associations between these genetic variants and cessation in multiple samples suggest a valid relation between these variants and cessation in some environmental contexts. Third, the smoking reports in the ARIC sample were not supported by biochemical confirmation. However, such confirmation was obtained in the UW-TTURC trial, and research shows that self-report is a valid indicant of current smoking, especially when there are no strong incentives to deceive (38).
