No difference in allele frequencies was observed between opioid-dependent and control groups with a pooled OR (95% CI) of the 16 studies of 1.16 (0.91–1.47), P = 0.23 (Figure 4). There was no evidence of publication bias within 16 articles included as indicated by the funnel plot (Figure 5) and Egger’s test value (t = 0.14, P = 0.89). Similar to genotype frequencies, significant heterogeneity existed between studies (I-squared = 74.7%; χ2 (15) = 59.40, P < 0.0001). Meta-regression analysis again failed to identify significant moderating effects for: 50% or more participants being Caucasian (yes/no) P = 1.0; 50% or more participants being Asian (yes/no) P = 0.50; mean age (continuous) P = 0.17; or type of dependence (opioid/heroin) P = 0.89. However, distinct from the genotype analysis, the percentage of males in the study was found to be a significant predictor of the log OR (P = 0.023), such that as the percentage of males in the study increased by 1 the OR increased by an average of 1.8%.
