In this study we identified distinct variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster that influence the age at onset of habitual smoking in young adults. These variants are not in LD with rs16969968 or its correlates that are associated with nicotine dependence. Earlier Schlaepfer and coworkers [32] also showed that variants other than rs16969968 or its correlates affect age at initiation of tobacco use at early age. These results show that there may be different mechanisms, which promote smoking behaviors at younger ages. The age dependent interplay of nicotinic receptors subtypes could explain the process of initiation to persistence of chronic smoking behaviors, but there remains a need for follow-up studies to confirm the hypothesis.
