Substance Use Disorder Liability: Candidate Gene System

该中心的这一新组成部分旨在阐明一大组基因 全面代表参与药物相关过程的神经生物学系统在物质使用障碍（SUD）风险中发挥作用。同时进行的遗传学调查的主要 已经显示在药物相关行为和药物反应中协同工作的神经化学系统将利用假设驱动的研究，同时具有与病因机制的复杂性相称的广泛范围。系统的方法可以大大增加检测到真正的遗传关联的先验概率，将这些发现的背景下，当前和不断扩大的神经生物学知识，并将它们与广泛的发展心理，精神病理学，生物学和环境信息的大样本CEDAR科目。CEDAR的高风险/家庭设计和独特丰富的纵向数据和大样本使最先进的遗传学方法能够应用于SUD易感性表型的定性（诊断）和定量定义，以及其发展的潜在生物行为介质。两 将使用基于家族和分层校正的基于群体（基因组对照）的分析方法。功能性神经化学研究将检查发现的遗传关联的生物学基础。由于CEDAR的儿童的很大一部分将在接下来的五年内进入SUD风险的模态年龄，因此将探索从物质使用到SUD的过渡以及风险的代际传递的遗传贡献。

This new component of the Center seeks to elucidate the role that a large set of genes comprehensively representing neurobiological systems involved in drug-related processes plays in the risk for substance use disorders (SUD). The concurrent genetic investigation of the major neurochemical systems that have been shown to work in concert in drug-related behavior and in drug response will take advantage of hypothesis-driven research while having a wide scope commensurate with the complexity of etiologic mechanisms. The systemic approach can considerably increase the prior probability of detecting true genetic associations, place these findings in the context of current and expanding neurobiological knowledge, and relate them to the extensive developmental psychological, psychopathological, biological, and environmental information available on the large sample of CEDAR subjects. CEDAR's high-risk / family design and uniquely rich longitudinal data and large sample enable application of the state-of-the-art genetic methods to qualitative (diagnostic) and quantitative definitions of the SUD liability phenotype, as well as to potential biobehavioral mediators of its development. Both family-based and stratification corrected population-based (genomic control) analytic approaches will be used. Functional neurochemical studies will examine the biological substrate of the genetic associations found. Since a substantial portion of CEDAR's children will enter the modal age of SUD risk in the ensuing five-year period, the genetic contribution to the transition from substance use to SUD as well as to the intergenerational transmission of the risk will be explored.