Phenogenetics of Liability to Substance Use Disorders

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DESCRIPTION (provided by applicant): Variation in the risk for abuse of and dependence on illicit substances (substance use disorders, SUD) is determined by multiple genetic and environmental factors. The etiology and pathogenesis of these complex disorders involve many facets of biological function (e.g., biochemical, physiological, behavioral, etc.), effects of abusable drugs on brain neurochemistry, and multiple environmental influences, and unfold throughout the life. Contribution of and interactions between these systems at the genetic level, as well as with environmental factors, need to be taken into account in research to comprehensively explicate SUD. The overarching aim of this Independent Scientist Award (K02) application is to integrate neurobiological, genetic, psychological and environmental information to elucidate the individual trajectory to SUD. Emphasis is placed on improving understanding of the relation between genetic and neurobiological processes as components of individual liability. To achieve this goal, expertise will be acquired in the developmental neurobiology of SUD that can be integrated with advanced genetic analysis of complex traits. Research will thus focus on empirically-based selection of genes within candidate neurobiological systems, and analysis of their association with the risk for SUD using quantitative trait indices of liability. To conduct this interdisciplinary research, I will access the consolidated database of Center for Education on Drug Abuse Research's (CEDAR; P50DA005605) and its genetic grogram, R01DA019157 "Substance Use Disorder Liability: Candidate Gene Systems" (CGS) consisting of multidisciplinary family data encompassing genetic, biochemical, psychological, psychiatric and environmental factors prospectively in target children at ages 10-12, 16, 19, and 22. The applicant is the Center's Co-Pi and Scientific Director as well as PI of the CGS project.