Meta-analysis of the per-allele association of rs1051730–rs16969968 genotype on unadjusted cotinine levels among current smokers indicated strong evidence of association (Figure 2). Pooling the six studies within a random effects framework indicated that the risk allele was associated with increased cotinine levels (mean increase in cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The between-study heterogeneity was low and not statistically significant (I2 = 23%, Pheterogeneity = .26). Following adjustment for self-reported cigarette consumption, the per-allele estimate was reduced by only 18% (mean increase in cotinine levels per allele = 113.76 nmol/L, 95% CI = 76.88 to 150.64 nmol/L, P = 1.49 × 10−9). Between-study heterogeneity remained low and was not statistically significant (I2 = 16%, Pheterogeneity = .31). No evidence for a difference between the estimates for the unadjusted and adjusted analyses was observed (P = .37) (not shown in the figure).
