Age at onset of regular smoking is a heritable trait consistently documented by twin studies, and it is influenced by environmental exposures, such as parental smoking and peer smoking.37 In addition, there is evidence from twin studies for a shared susceptibility to early-onset smoking and nicotine dependence.37 Therefore, it is interesting that we did not observe a direct association between rs16969968 and age at onset. Further analyses suggest that this result is robust to adjustment for sex, age, and coding of age at onset. We cannot rule out the possibility that unmeasured variables suppressed a true association between rs16969968 and age at onset. Further study is warranted to investigate the relationship between early smoking behaviors and genes in this region to improve our understanding of the mechanism by which age at onset modifies the genetic association with heavy smoking.
