Our investigation provides further evidence that OPRD1 polymorphisms are associated with risk for heroin dependence. Although the strongest observed signal involves intronic SNPs, support is found for potential functionality including either epigenetically-mediated mechanisms (Fujita et al. 2011) or via rs2236855’s status as an eqtl for other genes (Zeller et al. 2010). Our post-hoc finding that greater risk is associated with the less prevalent rs2236857-rs581111 haplotype suggests the importance of additional genotyping to determine the identity of an underlying functional polymorphism. The lack of significant association observed for any SNPs in OPRM1 and OPRK1 provides a striking contrast to the OPRD1 findings. Overall, our results support prioritizing research aimed at increasing current understanding of the important role played by OPRD1 in the pathophysiology of heroin dependence including ongoing efforts focusing on improved opioid drug design (Berger & Whistler 2010).
