NEUROGENETICS MODULEL

该中心的这个新组成部分旨在阐明一组全面代表药物相关过程中涉及的神经生物学系统的基因在物质使用障碍（SUD）风险中的作用。已被证明在药物相关行为和药物反应中协同工作的主要神经生物学系统的遗传学研究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，使国家的最先进的遗传学方法的应用，以定性（诊断）和定量定义的SUD的责任表型，以及潜在的生物行为介质和环境调节剂的发展。将使用基于家族和分层校正的基于人群（基因组对照）的分析方法，同时考虑性别和种族变异。功能性神经化学和功能性磁共振成像研究将检查发现的遗传关联的生物学基础。由于CEDAR的大多数儿童将在随后的五年内经历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 genetic investigation of the major neurobiological 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 and environmental moderators of its development. Both family-based and stratification-corrected population-based {genomic control) analytic approaches will be used, taking into account sex and ethnic variation. Functional neurochemical and fMRI studies will examine the biological substrate of the genetic associations found. As the majority of CEDAR's children will pass through 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.