In conclusion, our study further supports the role of genetic variation within CHRNA5-CHRNA3-CHRNB4 and TTC12-ANKK1-DRD2 gene-clusters on smoking and suggests that they are involved in different stages of the multi-step process leading to nicotine addiction. Variation at TTC12-ANKK1-DRD2 seems to influence risk of smoking in adulthood via its effect on smoking in adolescence and via increased novelty seeking. In contrast, genetic variation at CHRNA5-CHRNA3-CHRNB4 seems mainly involved in the transition towards heavy use in mid-adulthood and in smoking persistence. Further studies are needed to identify new genetic loci moderating smoking behavior in adolescence and early adulthood.
