This project, the first collaborative genetic meta-analysis to investigate specific and general liability for these substance dependence diagnoses, has demonstrated that the G allele of rs1799971 has a modest protective effect on general substance dependence liability (OR = 0.90, 95% C.I. (0.83–0.97), p-value =9.52 × 10−3) in samples of European ancestry. This is the first meta-analysis to show that this non-synonymous variant, which has been heavily studied for functional effects, is significantly associated in European ancestry samples with liability to substance dependence. The small but significant effect size of rs1799971 suggests that variability in previous association reports may be due in part to sampling variation. This collaborative meta-analysis benefited from the opportunity to define uniform phenotypes across studies, perform coordinated, de novo analyses to test our hypotheses, and include existing datasets that have not yet focused on the question of rs1799971 and addiction.
