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Aims: The main aim of the study was to test the moderating effect of two genetic polymorphisms, one in the dopamine D2 receptor gene (DRD2) and one in the mu-opioid receptor gene (OPRM1), on the link between parental rule-setting and adolescent alcohol use. Methods: A total of 214 adolescents (Mage =13.7, 44.9% male) provided saliva samples and completed survey items describing alcohol use and parental rule-setting. Results: Findings indicated that alcohol-specific parental rule-setting was more robustly associated with alcohol use for adolescents with the DRD2 A1 risk allele and for those with the OPRM1 G-allele. Conclusion: This study replicates the interaction between parental rule-setting and the DRD2 risk allele on adolescent alcohol use and extends the literature by demonstrating the moderating effects of the OPRM1 risk allele on the link between parental rule-setting and adolescent alcohol use. [ABSTRACT FROM AUTHOR]