Our investigation compared a large sample of heroin dependent cases to individuals with no history of illicit drug or alcohol dependence and found a strong association of four OPRD1 SNPs with heroin dependence. The estimates of risk (odds-ratio 1.25) for the two most highly associated SNPs, rs2236855 and rs2336857, are of similar magnitude to those observed with other complex traits. The degree of LD observed between these SNPs and most of the other nominally-associated OPRD1 polymorphisms is consistent with a single strong signal. These results replicate the findings of a prior report (Levran et al. 2008) which also used Illumina GoldenGate technology to genotype 1536 SNPs (including OPRM1, OPRD1, and OPRK1 polymorphisms) in similarly ascertained cases (412 heroin dependent individuals on methadone maintenance therapy in the U.S. and Israel) and controls (184 individuals screened as having no substantial history of illicit drug or alcohol use). The nine SNPs that were most strongly associated with heroin dependence in their sample included three OPRD1 SNPs, all of which were genotyped in the current report (see Supplementary Table 4). Two (rs2236857 and rs3766951)
