At the haplotype level, in the three long-term EA smoker cohorts recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, Weiss et al. [19] found that a 5-SNP haplotype HA (CCAGA) formed by rs680244-rs569207-rs16969968-rs578776-rs1051730 (denoted EA_H1), had a risk effect on high FTND score (>6) compared with low FTND score (<4) (OR = 1.50, 95% CI: 1.21, 1.86, P = 1.3×10−4), and the 5-SNP haplotype HC (CTGAG) formed by the same SNPs as in HA had a protective effect on high ND (OR = 0.66, 95% CI: 0.52, 0.85, P = 1.07×10−3). Such findings corroborated for ND assessed by Primary Dependence Motives (PDM) score [46]. Further, our previous study in the Mid-South Tobacco Family (MSTF) cohort revealed 3 additional haplotypes in EAs [18], formed by rs6495308-rs3743075-rs8040868 (EA_H2), rs3743075-rs8040868-rs6495309 (EA_H3), and rs17408276-rs16969968-rs615470 (EA_H4), that were associated with smoking-related phenotypes. In comparison with EA_H1, although EA_H4 was physically encompassed by EA_H1, and they share 1 SNP (i.e., rs16969968), EA_H2 and EA_H3, which have 2 overlapping SNPs (i.e., rs3743075 and rs8040868), were physically separate from EA_H1. Also in the MSTF cohort,
