To assess ND, various scales have been developed, which include the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria [4], Fagerström Test for ND (FTND) [37], HSI [38], the Nicotine Dependence Syndrome Scale (NDSS) [39], and the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) [40], to name a few. Among them, FTND is the most widely used instrument, primarily because of its succinctness and ease of administration [41]. The FTND score is commonly treated as a continuous variable, and an FTND ≥4 is typically defined as highly dependent [28], [42]. CPD, the most commonly used consumption measure [38], is both highly heritable [7] and predictive of ND [24], [38]. SQ is an ordinal variable based on CPD, which provides a simple, quantified index of the amount of cigarette consumption. It should be noted that SQ and FTND are correlated but different psychometric measures of smoking behavior. To date, associations of variants in the CHRNA5/A3/B4 cluster with smoking have been detected for both SQ and FTND phenotypes, but signals appear to be stronger for SQ than for FTND (Figure 2), which is also true for linkage study on ND based on a review of more than 20 independent studies [43].
