Genetics are presumed to contribute 30-40% to opioid use disorder (OUD), allowing for the possibility that genetic markers could be used to identify personal risk for developing OUD. We aimed to test the potential association among 180 candidate single nucleotide polymorphisms (SNPs), 120 of which were related to the dopamine reward pathway and 60 related to pharmacokinetics. Participants were randomly recruited in 2020-2021 in a cross-sectional genetic association study. Self-reported health history including Diagnostic and Statistical Manual of Mental Disorders (DSM-5) OUD criteria and buccal swabs were collected. A total of 1,301 participants were included in the analyses for this study. Of included participants, 250 met the DSM-5 criteria for ever having OUD.

Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and DSM-5 criteria consistent with OUD. Six SNPs found in four genes were associated with OUD: increased odds with CYP3A5 and DRD3, and decreased odds with CYP3A4 and CYP1A2. Homozygotic CYP3A5 had the highest adjusted odds ratio of 2.812 and 2.495, respectively. Variants within the dopamine reward and opioid metabolism pathways have significant positive (DRD3 and CYP3A5) and negative (CYP3A4 and CYP1A2) associations with OUD. Identification of these variants provides promising possibilities for genetic prognostic and therapeutic targets for future investigation.