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Chunk #18 — Results — CHRNA5-A3-B4 Haplotype Effects

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A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction.
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To ensure that the obtained results were not dependent upon the particular age of daily smoking onset or FTND dichotomy that was used, the effects for both phenotypes were investigated in more detail. First, the interaction between haplotype and age of onset as a continuous variable was tested based on the combined UT-WI-LHS cohorts and using FTND46 as the dependent variable. The HA vs. HC by daily age interaction effect was significant, p = 0.01, OR = 0.95 (95% CI = 0.91–0.99), but the HB vs. HC interaction effect was not significant, p = 0.24, OR = 0.98 (95% CI = 0.94–1.02). Next, subjects where divided into quartiles based on onset age of daily smoking and the haplotype effects within each quartile were tested separately. Table 5 shows the logistic regression analysis for the HA vs. HC effect was significant in the two younger quartiles (p = 0.0003 for 15–16 years and p = 0.01 for <15 years), but not in the two older quartiles (p = 0.43 for 17–18 years and p = 0.63 for >18 years). Figure 3 shows the relative haplotype frequencies across each age group quartile.