It is worth noting that to establish a replication of a genotype–phenotype association, every effort should be made to analyze phenotypes comparable to those reported in the original study.29 However, the ND genetics studies mentioned above involved a plethora of smoking-related phenotypes. Generally speaking, they can be classified into the following groups: 1) categorical variables along smoking trajectories; e.g., smoking initiation, status, and cessation; 2) ND assessed using DSM-IV or FTND; 3) smoking quantity such as CPD; and 4) endophenotypes such as NMR, cotinine and CO concentrations, or functional imaging results. At least two of the four phenotype groups have been used in genome-wide linkage studies (Table 1),34 candidate gene association studies (Table 2), and GWASs (Table 3). Because of the sample source and size requirement differences, DSM- or FTND-ascertained ND definitions were commonly used in linkage studies, whereas CPD 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
