rs581111 (also located in intron 1) in an analysis conditioned on the most strongly associated SNP, found evidence of an association stronger by more than an order of magnitude (uncorrected p=1.41 × 10−5). These results are suggestive of a non-genotyped SNP with a less prevalent minor allele (the GA haplotype frequency is 0.077), associated with substantial heroin dependence risk (OR 1.68), the identification of which could likely be achieved using currently available approaches such as deep sequencing. Given that this polymorphism is apparently located in an intronic region, its effects may involve altered OPRD1 expression [e.g., see (Lomelin, Jorgenson, & Risch 2010)]. Ongoing research examining the regulation of OPRD1 expression (Tuusa, Leskelä, & Petäjä-Repo 2010) and DOR trafficking (Bie et al. 2010) will also help guide further investigation.
