We observed a significant association between rs1799971 and general substance dependence (Figure 1). Based on 9064 cases and 7844 age-filtered controls from 20 datasets, the G allele showed a modest protective effect (OR = 0.90, 95% C.I. [0.83–0.97], p-value = 9.52 × 10−3, N = 16,908); 15 of the 20 studies showed a protective direction of the G allele. Heterogeneity variance was not statistically significant (Q=20.13, p-value = 0.39). A secondary analysis that did not require controls to be over 25 years old yielded a similar odds ratio (OR = 0.90, 95% C.I. (0.84–0.98), N = 17,918), but was not statistically significant after multiple correction in this larger sample (p-value = 1.06×10−2), consistent with our hypothesis that it is important for controls to be past the typical age of risk.
