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)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多个方面(如生化、生理、行为等)，以及滥用药物对脑神经化学的影响，以及多种环境影响，并贯穿于整个生命过程。在研究中需要考虑这些系统在遗传水平上的贡献和相互作用，以及与环境因素的相互作用，以全面阐明SUD。 这一独立科学家奖(K02)申请的首要目标是整合神经生物学、遗传学、心理学和环境信息，以阐明个体到SUD的轨迹。重点是加强对作为个人责任组成部分的遗传和神经生物学过程之间的关系的理解。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，该专业知识可以与复杂性状的高级遗传分析相结合。因此，研究将集中在候选神经生物学系统中基于经验的基因选择，并使用风险的量化特征指数分析它们与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(Cedar；P50DA005605)的综合数据库及其遗传图R01DA019157“物质使用障碍责任：候选基因系统”(CGS)，其中包含多学科的家庭数据，包括预期年龄为10-12岁、16岁、19岁和22岁的目标儿童的遗传、生化、心理、精神和环境因素。申请者是该中心的联合PI和科学主任，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.