The impact of the TTC12-ANKK1-DRD2 on smoking behavior was stronger in adolescence (OR for TTC12-rs10502172[G] ~1.30) than mid-adulthood (OR~1.15). This result suggests that TTC12-ANKK1-DRD2 impact on smoking behavior tends to decrease over time. Further supporting this hypothesis, TTC12-rs10502172[G] effect in adulthood was entirely mediated by its effect on smoking in adolescence and by high novelty seeking, a temperamental trait that is characterized by increased tendency to experiment psychotropic substances and that tends to decline with age(25, 56). Indeed, at age 31, TTC12-rs10502172[G] was found in excess among ex-smokers, indicating that not all individuals carrying this risk variant and initiating smoking in adolescence continue smoking in adulthood and that other genetic and/or environmental factors are likely to influence smoking persistence.
