The relationship among smoking, genotype, and age at onset of smoking is detailed in Figure 2. Consistent with previous work, early onset of smoking and rs16969968 contribute to the risk of heavy smoking. Initiating smoking earlier than 16 years of age is significantly associated with higher risk of heavy smoking (OR = 2.63, unadjusted for genotype; 95% CI, 2.49–2.78; P < .001). The A allele at rs16969968 is associated with a higher risk of heavy smoking (OR=1.28 per A allele, unadjusted for age at onset; 95% CI, 1.25–1.32; P < .001, modeled additively). The interaction between early-onset smoking and the A allele at rs16969968 is 1.16 (P =.01), with OR=1.27 in late-onset smokers compared with OR = 1.46 in early-onset smokers. In Figure 2, the interaction is illustrated by the larger differences between bar heights in the early-onset data compared with the late-onset data, corresponding to a larger genetic effect in the early-onset group.
