Diplotype analyses also suggest that age-of-onset moderates the relation of these variants with nicotine dependence (Figure 2). Logistic regression analysis in the combined sample showed a significant interaction between the diplotype status (AA vs. BC) and age-of-onset (P = 0.02, OR = 0.43, 95% CI 0.86 to 0.21). Analyses in the early onset group found significant differences between diplotype AA and all other tested diplotypes (P value range from 0.05 to 3.0×10−4). The contrast between diplotype AA vs. diplotype AC (P = 0.03, OR = 0.53, 95% CI 0.93 to 0.30) and diplotype AA vs. diplotype BC (P = 3.0×10−4, OR = 0.35, 95% CI 0.62 to 0.20) suggests a recessive effect of Haplotype A, and an incomplete dominance effect of Haplotype C (Figure 2A).
