All the smoking-related diseases with observed associations with rs1051730/rs16969968 show some evidence of association with R336C (Table 2), and the effects are larger for early-onset groups. Many of the phenotypes tested are correlated, such that the individual associations with the different smoking-related diseases cannot be considered independent. To assess the overall significance of the effect that the variant has on the smoking-related diseases we combined the lists and assessed the whole group for association with R336C. This is justified by the fact that the difference between the smoking-related diseases can be looked upon as variation in expressivity of one environmental factor, namely tobacco smoke. The overall P-values obtained from this analysis are 6.8 × 10−5 and 2.1 × 10−7 for the total and early-onset smoking-related diseases, respectively, providing an estimate of the combined strength of the evidence for association with the health consequences of smoking (Table 2).
