This study has several limitations. First, the sample is limited in several ways. When multiple genetic markers are analyzed, the sample size in certain conditions becomes small, so these effect size estimates should be considered as preliminary. This sample is the same as that used in the Chen et al. study(1), thus this research does not provide new evidence to support the relation of CHRNA5 with cessation outcomes. This study focuses on only European-Americans. Second, one could surmise that smoking quantity plays a mediating role in our reported association between CYP2A6 and cessation (28). We showed that CYP2A6 remained significantly associated with smoking outcomes, suggesting that it could influence biological processes underlying both smoking quantity and smoking cessation (22, 29, 30). However, self-reported smoking rate is an imperfect measure of actual smoking heaviness (31, 32) and future research would benefit from the use of sensitive biomarkers of tobacco exposure. Future studies of mechanisms require biomarkers such as cotinine levels. The mechanisms underlying CYP2A6 and smoking cessation is not entirely clear, the complex genetic architecture in this chromosomal region and other
