Neuropharmacological and neurogenetic correlates of opioid use disorder (OUD) as a function of ethnicity: Relevance to precision addiction medicine

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Background: Over 100 people die daily from opioid overdose and $78.5B per year is spent on treatment efforts, however, the real societal cost is multifold greater. Alternative strategies to eradicate/manage drug misuse and addiction need consideration. The perception of opioid addiction as a social/criminal problem has evolved to evidence-based considerations of them as clinical disorders with a genetic basis. We present evaluations of the genetics of addiction with ancestry-specific risk profiles for consideration. Objective: Studies of gene variants associated with predisposition to substance use disorders (SUDs) are monolithic, and exclude many ethnic groups, especially Hispanics and African Ameri-cans. We evaluate gene polymorphisms that impact brain reward and predispose individuals to opioid addictions, with a focus on the disparity of research which includes individuals of African and Hispanic descent. Methodology: PubMed and Google Scholar were searched for: Opioid Use Disorder (OUD), Ge-nome-wide association studies (GWAS); genetic variants; polymorphisms, restriction fragment length polymorphisms (RFLP); genomics, epigenetics, race, ethnic group, ethnicity, ancestry, Cau-casian/White, African American/Black, Hispanic, Asian, addictive behaviors, reward deficiency syndrome (RDS), mutation, insertion/deletion, and promotor region. Results: Many studies exclude non-White individuals. Studies that include diverse populations report ethnicity-specific frequencies of risk genes, with certain polymorphisms specifically associated with Caucasian and not African-American or Hispanic susceptibility to OUD or SUDs, and vice versa. Conclusion: To adapt precision medicine-based addiction management in a blended society, we propose that ethnicity/ancestry-informed genetic variations must be analyzed to provide real preci-sion-guided therapeutics with the intent to attenuate this uncontrollable fatal epidemic.

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