the association is with regulatory variation in the gene. Non-coding OPRK1 variations have also been associated with opioid addiction (20), as was the coding SNP G36T (21). The association of variants in PDYN with alcohol dependence was also replicated (22). Variations in other opioid receptor genes were not associated with alcohol dependence in the same large, family-based sample in which the association with OPRK1 was reported (17). The involvement of genes encoding both an opioid receptor (OPRK1) and its ligand (PDYN) makes biological sense, indicating that variations in signaling through this system, by varying either the ligand or receptor, affect alcohol consumption and alcohol dependence.
