Figure 1 shows the meta-analysis forest plots for the association between heavy vs light smoking and the rs16969968 A allele, stratified by early- and late-onset smoking. Specifically, this meta-analysis tests whether the genetic risk for heavy smoking, based on the rs16969968 A allele, is different between early- and late-onset smokers (n=33 348). Smokers in the intermediate smoking level were excluded (CPD of 11–20). Compared with individuals with the rs16969968 GG genotype (wild-type allele), the odds ratio (OR) in early-onset smokers was 1.45 (95% CI, 1.36–1.55) for individuals with AG genotypes and 2.10 (95% CI, 1.97–2.25) for individuals with AA genotypes. In late-onset smokers, the OR is 1.27 (95% CI, 1.21–1.33) for individuals with AG genotypes and 1.61 (95% CI, 1.54–1.69) for individuals with GG genotypes. The difference between the OR in early-onset smokers and the OR in late-onset smokers is significant (P =.01). However, the current model does not adequately capture the heterogeneity among data sets: the heterogeneity χ2 value (Q′) was calculated to be 117 (P<.001, 69 df).
