A logical case can be made for there being a relation between the CHRNA5-CHRNA3-CHRNB4 variants and smoking cessation. These variants are consistently related to measures of smoking heaviness and nicotine dependence (12, 16), and there is copious evidence that measures of nicotine dependence predict cessation likelihood (4, 5, 24). These findings encourage an examination of the involvement of the CHRNA5-CHRNA3-CHRNB4 variants with cessation, and further suggest that this relation will be mediated by dependence. If evidence for mediation is not found, and yet the variants are related to cessation, it would suggest that the variants influence cessation via routes that are independent to their influence on dependence. Moreover, previous research suggests that the relation between the CHRNA5-CHRNA3-CHRNB4 variants and cessation should be examined with regard to pharmacotherapy. There is mounting evidence that pharmacotherapies work by mitigating the risks for cessation failure that are related to severity of nicotine dependence (25, 26). This suggests that the connection between the variants and cessation may be strongest amongst individuals who do not receive pharmacotherapy for smoking cessation.
