rs678849

This review examines neurogenetic and neuropharmacological correlates of opioid use disorder (OUD) with emphasis on ancestry-specific genetic risk profiles. The paper identifies multiple genes involved in the reward pathway (DRD2, DRD3, DRD4, OPRM1, OPRK1, OPRD1, BDNF, NRXN3, COMT, SLC6A4, KCNC1, KCNG2) and their variants associated with OUD susceptibility and treatment response across different ethnic populations, highlighting critical research disparities where African Americans and Hispanics have been underrepresented in genetic association studies.

This association study identified rs678849 in the delta opioid receptor gene OPRD1 as being associated with smaller regional brain volumes in the ADNI cohort of 738 elderly participants, with replication in the QTIM cohort of 578 young adult twins. The C allele at rs678849 predicted reduced volumes in frontal, temporal, and occipital brain regions (P = 7.74 × 10⁻⁵ in ADNI). In healthy elderly, the C allele was also associated with elevated cerebrospinal fluid neurodegenerative biomarkers (P = 0.027 for t-tau/Aβ42 ratio).