Another noteworthy finding is that the effect of the non-synonymous coding SNP rs16969968 in CHRNA5 appears to be more important in later onset smokers. This contrasts with the findings of Weiss and colleagues, who suggested that haplotypes involving this polymorphism were more important among early onset smokers (Weiss et al. 2008). There are a number of differences in phenotype definitions, sampling approaches, and comorbidity between our sample and that of Weiss and colleagues; however there is no obvious reason for the clear discrepancy between findings. It is noteworthy that a significant interaction appeared in both samples, but further examination in larger samples and across populations will be required to discern the functional significance of this interaction, if any. The confidence intervals for this interaction parameter are close to 1.0 (0.89, 0.99), whereas interaction parameter estimates for some other SNPs were more robust (e.g., GRIN2B and ADCY8). Differences in sampling, secular trends in environmental contributions to nicotine dependence, as well as random fluctuation could all contribute to discrepancies in estimates of effect sizes.
