Despite having an important role in the development of nicotine dependence among daily smokers, variation in CYP2A6 was not associated with smoking initiation nor the progression to daily smoking (step 1 in Figure 3). Previous twin studies support that environmental influences primarily drive early adolescent nicotine use, and that the role of heritable factors on smoking behaviors increases throughout young adulthood (Kendler et al., 2008; Koopmans et al., 1999). Our results are consistent with this model by providing evidence of a specific gene that impacts the transition from daily smoking to nicotine dependence, without influencing initiation and daily smoking.
