Nonetheless, the use of an AGRS approach may provide fresh insight into the mixed findings in the smoking cessation literature when a single variant is examined in isolation. Although it has long been known in the animal literature that genetic alterations may have different effects on phenotype depending upon the strains used, this approach is among the earlier attempts to account for the genetic ‘background’ that may influence single polymorphism investigations in humans. This concept is nicely demonstrated in a study of the genetic contributions to pain wherein main effects of a single variant are obscured when confounding influences of other associated polymorphisms are not accounted for.6 It is important to note however that the AGRS approach in this instance is completely dependent upon prior studies performed to examine single polymorphisms, which speaks to the need for continued efforts in this area. It is conceivable that a more broadly-based AGRS that included additional variants implicated by bupropion’s pharmacology would have improved the ability of the AGRS to moderate treatment. As sufficient sample sizes are gathered to allow more atheoretical variant
