of an associating variant to a specific trait. Causal mediation analysis has been used to improve the understanding of the mechanisms underlying detected associations (Jiang et al. 2013; Liu et al. 2013). The estimation of mediation effects in the context of survival models has been discussed in previous literature (Lange and Hansen 2011; VanderWeele 2011; Nemes et al. 2013). Smoking behavior is likely influenced by a variety of additional factors besides the function of nicotinic receptors and nicotine metabolism, such as psychiatric disorders (e.g., schizophrenia, depression) and somatic consequences of smoking (e.g., bronchitis, chronic obstructive pulmonary disease). Understanding the mechanisms underlying the progression of smoking behavior could facilitate the development of targeted cessation pharmacotherapies and interventions.
