was more often applied in GWAS. For candidate gene association studies, more comprehensive smoking profiles were usually tested for association with positive results from unbiased studies as replication, or more importantly, extension by using different phenotypes (Table 2), because there is considerable evidence that the various smoking measures are not highly related to one another.142 Even for measures with relatively high correlation, such as FTND and CPD, the slight change of phenotype from FTND-based ND to CPD would change the results.25 Therefore, although several loci, such as TTC12-ANKK1-DRD2, CHRNA5/A3/B4, and CYP2A6/B6 showed associations with different phenotypes (Tables 2 and 3), we should not expect positive associations with one phenotype to be replicated in samples with other phenotypes. It is important to keep in mind that a small change in phenotype may expose previously undiscovered variants, which underlie different biological processes and may have specific roles in distinguishing phenotypes.25
