Three consistent findings emerged with this division. First, the comparison of heroin-dependent cases to non-dependent neighborhood controls found three SNPs with p values significant after correction for multiple testing. Second, the comparison of cases to illicit drug-dependent neighborhood controls was remarkable for the complete lack of even nominally-significant differences for TTC12 and ANKK1 SNPs. Third, the comparison of non-dependent to illicit drug-dependent neighborhood controls found a pattern of association nearly identical to the comparison of the former with cases, with the smaller size of the latter sample limiting overall power. A post-hoc comparison of non-dependent neighborhood controls with a combined group of heroin-dependent cases and illicit drug dependent controls found significance improved incrementally for the association with rs877138 (p=6.4 × 10−7). Our results provide strong evidence that a block of ANKK1 and TTC12 SNPs in high LD is associated with heroin and other illicit drug dependence. The large difference in the strength of association observed in the comparison with non-dependent neighborhood controls (individuals with high exposure to illicit drugs, either via use or from residing in environments with widespread drug
