Phenogenetics of Liability to Substance Use Disorders

描述（由申请人提供）： 滥用和依赖非法物质（物质使用障碍，SUD）的风险变化是由多种遗传和环境因素决定的。这些复杂疾病的病因和发病机制涉及生物功能的许多方面（例如，生物化学、生理学、行为学等），滥用药物对大脑神经化学的影响，以及多种环境影响，并在整个生命中展开。这些系统在遗传水平上的贡献和相互作用，以及与环境因素，需要在研究中考虑到全面解释SUD。 这项独立科学家奖（K 02）申请的总体目标是整合神经生物学，遗传学，心理学和环境信息，以阐明SUD的个人轨迹。重点放在提高对遗传和神经生物学过程作为个人责任的组成部分之间的关系的理解。为了实现这一目标，将获得SUD发育神经生物学方面的专业知识，这些知识可以与复杂性状的先进遗传分析相结合。因此，研究将集中在候选神经生物学系统内的基因选择，并使用责任的定量性状指数分析它们与SUD风险的关联。 为了进行这项跨学科的研究，我将访问药物滥用研究教育中心的综合数据库，（CEDAR; P50 DA 005605）及其遗传程序，R 01 DA 019157“物质使用障碍责任：候选基因系统”（CGS）包括多学科的家庭数据，包括遗传，生化，心理，在10-12岁、16岁、19岁和22岁的目标儿童中前瞻性地研究精神和环境因素。申请人是该中心的合作PI和科学总监以及CGS项目的PI。

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.