Etiological research on substance abuse highlights the importance of progression from initiation to heavy use during adolescence in the development of dependence in adulthood.52,53 In this study, we linked the developmental progression of smoking behavior to genetic risk. We derived a genetic risk score (GRS) from GWAS of smoking quantity. This GRS was not related to smoking initiation. In fact, daily smokers who did not progress to heavy use were at lower genetic risk than individuals who never smoked. Among individuals who initiated smoking, those at higher genetic risk progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting. Critically, high genetic risk led individuals to become persistent heavy smokers, nicotine dependent, and unable to quit only to the extent that they progressed rapidly from smoking initiation to heavy smoking during adolescence.
