Opioid dependence (OD) is a common, chronic, relapsing addiction with a substantial genetic component.Central to the neurobiology of OD is the mu opioid receptor (MOR), through which most of the rewardingeffects of opioids are mediated. The goal of this project is to enhance our understanding of MOR in ODthrough linkage disequilibrium (LD) genetics studies of OD, using novel candidate genes, MOR interactingproteins (MORIPs). MOR exists as a complex with multiple binding partners (MORIPs) which mediate thesignal transduction process, as well as receptor trafficking and desensitization.Relatively few MORIPs are known. Using existing MORIPs as well as novel ones identified through anindependent collaboration, we will conduct a case-control association analysis of these known MORIPs andnewly-defined MORIPs. We have assembled a set of DNA samples and clinical information from ~ 1500 ODindividuals, whose data and biopecimens are in a central NIDA repository. In addition, we have access to ~4500 control DNA samples and clinical information from an NIMH repository. Using these resources, MORIPgenes will be assessed for roles in genetic susceptibility to OD. Through this project, our understanding ofthe role of MOR in OD will be enhanced, opening new avenues for treatment of this common and severeaddiction.
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