The genetic epidemiology of substance use disorder: A review

Background: Substance use disorder (SUD) remains a significant public health issue. A greater understanding of how genes and environment interact to regulate phenotypes comprising SUD will facilitate directed treatments and prevention. Methods: The literature studying the neurobiological correlates of SUD with a focus on the genetic and environmental influences underlying these mechanisms was reviewed. Results from twin/family, human genetic association, gene-environment interaction, epigenetic literature, phenome-wide association studies are summarized for alcohol, nicotine, cannabinoids, cocaine, and opioids. Results: There are substantial genetic influences on SUD that are expected to influence multiple neuro-transmission pathways, and these influences are particularly important within the dopaminergic system. Genetic influences involved in other aspects of SUD etiology including drug processing and metabolism are also identified. Studies of gene-environment interaction emphasize the importance of environmental context in SUD. Epigenetic studies indicate drug-specific changes in gene expression as well as differences in gene expression related to the use of multiple substances. Further, gene expression is expected to differ by stage of SUD such as substance initiation versus chronic substance use. While a substantial literature has developed for alcohol and nicotine use disorders, there is comparatively less information for other commonly abused substances. Conclusions: A better understanding of genetically-mediated mechanisms involved in the neurobiology of SUD provides increased. opportunity to develop behavioral and biologically based treatment and prevention of SUD.