analysis using smokers and non-smokers that included the two CHRNB2 3′ UTR SNPs and rs2236196 at CHRNA4 to detect gene–gene interactions associated with nicotine dependence failed to detect significant interaction (41). However, nicotine dependence only modestly predicts smoking cessation in response to bupropion (4) and twin studies of the genetic relationship between the two phenotypes suggest that the two phenotypes may have differing genetic contributions [reviewed by Lessov-Schlaggar et al. (42)]. Of note, neither the genes in the dopamine pathway examined here, including those implicated in prior studies, nor the CHRNA3/CHRNA5 gene cluster associated with nicotine dependence in recent reports (15,43–46) reached the threshold of significance for association with smoking cessation or treatment response.
