NEUROGENETICS MODULEL

神经遗传学模块

基本信息

批准号：
7813374
负责人：
MICHAEL M VANYUKOV
金额：
$ 39.16万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-15 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7813374
关键词：
Accounting Affect Affective Age Age-Years Alcohol or Other Drugs use Amygdaloid structure Arts Attention Behavior Behavioral Biological Brain Candidate Disease Gene Characteristics Child Clinical Cognitive DSM-IV Data Development Diagnosis Diagnostic Disease Drug Addiction Environment Environmental Risk Factor Family Fathers Female Functional Magnetic Resonance Imaging Funding Future Gene Expression Genes Genetic Genetic Polymorphism Genetic Variation Genome Scan Genomics Genotype Goals Heritability Illicit Drugs Individual Informal Social Control Interdisciplinary Study Investigation Knowledge Measurement Measures Mediating Mediation Mediator of activation protein Methaqualone Methodology Methods Modeling Motivation National Institute of Drug Abuse Neurobiology Neuronal Plasticity Neurotransmitters Outcome Pathway interactions Pharmaceutical Preparations Phenotype Physiology Play Positioning Attribute Probability Process Psychological reinforcement Psychopathology Regulation Research Resources Risk Role Sampling Science Self-control as a personality trait Severities Sex Characteristics Socialization Specificity Staging Stratification Structure Substance Use Disorder System Testing Translations Validation Variant Ventral Striatum Work addiction anti social base behavior measurement biobehavior biological adaptation to stress cohesion design disorder risk drug reward early childhood genetic analysis genetic association genome wide association study high risk indexing innovation intergenerational longitudinal design male member neurobiological mechanism neurochemistry neurogenetics neuroimaging neurotransmission novel offspring peer population based psychologic response sex statistics theories trait transmission process

项目摘要

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.

该中心的这个新组成部分旨在阐明一系列基因全面代表与药物相关过程涉及的神经生物学系统的作用。已证明在与药物有关的行为和药物反应中共同起作用的主要神经生物学系统的遗传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。系统性方法可以大大提高检测真正遗传关联的先验概率，将这些发现置于当前和扩大神经生物学知识的背景下，并将其与广泛的发育心理学，心理病理学，生物学，生物学和环境信息联系起来。 Cedar的高风险/家庭设计以及独特的纵向数据和大型样本，可以将最先进的遗传学方法应用于定性（诊断）和SUD责任表型的定量定义，以及潜在的生物行为介体和其发展的潜在生物行为中介体和环境调节剂。考虑到性别和种族差异，将使用基于家庭和分层校正的人群（基因组控制）分析方法。功能性神经化学和功能磁共振成像研究将检查发现的遗传关联的生物底物。由于大多数Cedar的孩子将在随后的五年内经历SUD风险的模态时代，因此将探索从物质使用到SUD的过渡以及风险的代际传播的遗传贡献。