Substance Use Disorder Liability: Candidate Gene System

该中心的这个新组成部分试图阐明一大组基因 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)的风险中发挥作用。少年儿童的同步遗传调查 已被证明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说驱动的研究，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发现真正遗传联系的先验概率，将这些发现放在当前和不断扩大的神经生物学知识的背景下，并将它们与在大样本雪松上可获得的广泛的发育心理学、精神病理学、生物学和环境信息联系起来。Cedar的高风险/家族设计以及独特丰富的纵向数据和大样本使最先进的遗传方法能够应用于对SUD易感性表型的定性(诊断)和定量定义，以及对其发展的潜在生物行为调节因素。两者都有 将使用基于家庭和分层修正的基于人口(基因组控制)的分析方法。功能神经化学研究将检查发现的遗传关联的生物底物。由于在接下来的五年时间里，雪松的大部分儿童将进入慢性阻塞性肺疾病的发病年龄，因此将探讨遗传因素对从药物使用向阻塞性睡眠呼吸暂停综合征的转变以及风险代际传递的影响。

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.