adulthood (Chenoweth et al., 2016). Cannon et al. (2016) followed 296 participants across ages 16–24 and found that using a CYP2A6 diplotype predictive metric, intermediate metabolism compared to slow and normal was a risk factor for smoking frequency and nicotine dependence. By the end of the study at age 24, however, the individuals with predicted normal metabolism were at greatest risk for these smoking behaviors. Many possible explanations exist for these discrepant results. One hypothesis is that the effect of slower nicotine metabolism transitions rapidly from increasing risk to being protective (Cannon 2016; O’Loughlin 2004), and previous studies may have observed different developmental periods in the fast-changing early course of smoking behaviors. The ascertainment of subjects and baseline smoking behaviors also varies across studies, which may influence the power to detect associations. Furthermore, previous studies use different measures of smoking behaviors and nicotine dependence, and it is possible that they capture different components of dependence that are differentially influenced by CYP2A6 metabolism.
