In our GWAS discovery cohort, control subjects were defined as never-smokers. This criterion for selecting controls is different from the conventional one, where current non-smoking subjects with a certain degree of previous exposure (e.g., having smoked more than 1 but less than 100 cigarettes in their lifetime) are normally selected as controls. Therefore, a potential problem of our study design is that some “control” subjects in our GWAS sample may in future become smokers if exposed to cigarettes. Depending on the number of such subjects, this potential misclassification problem may undercut the statistical power of our study, leading to false negative results. In our study, we tried to minimize the effects caused by this potential problem by excluding those control (non-smoking) subjects under the age of 25 from our study. Since most smokers initiate smoking behavior in adolescence, non-smoking subjects under the age of 25 may have a much higher chance than older people to develop smoking behavior if exposed to cigarettes. Therefore, after excluding these younger subjects from our control group, the subjects in the group that may later
