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Genetics of EEG Patterns in ADHD

ADHD 脑电图模式的遗传学

基本信息

批准号：
7760987
负责人：
Sandra K Loo
金额：
$ 33.42万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-15 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7760987
关键词：
Affect Attention Attention deficit hyperactivity disorder Behavior Behavior Disorders Behavioral Behavioral Symptoms Biological Blood Brain Candidate Disease Gene Child Chromosome Mapping Cognitive Complex Data Data Collection Data Linkages Daydreams Diagnostic Diagnostic Procedure Electroencephalography Family Fathers Freedom Frequencies Genes Genetic Genetic Heterogeneity Genetic Variation Genotype Goals Grant Heritability Heterogeneity Hyperactive behavior Impulsivity Intervention Interview Investigation Lead Link Measures Molecular Genetics Neurocognitive Neuropsychological Tests Parents Parietal Pathway interactions Pattern Performance Phenotype Polymorphic Microsatellite Marker Reaction Time Relative (related person)Research Research Personnel Risk Sampling Short-Term Memory Siblings Signal Transduction Sorting - Cell Movement Structure Susceptibility Gene Testing United States Variant Work affection brain behavior cost disorder subtype endophenotype gene discovery improved inattention indexing innovation offspring processing speed programs response segregation trait

项目摘要

Attention Deficit Hyperactivity Disorder (ADHD) is a complex behavioral disorder that affects an estimated 5-10% of children in the United States. Recent research in ADHD suggests it is a complex behavioral phenotype that is the result of genetic heterogeneity with sample differences likely reflecting variation in relative proportions of various susceptibility genes, their corresponding brain correlates, and background gene effects. Gene discovery and subsequent elucidation of gene to brain to behavior pathways can be facilitated if etiological heterogeneity is reduced (for example, through use of genetic isolates and/or selection through multiplex families) or if the phenotype can be refined into familial components that may be more closely linked to specific underlying risk genes (i.e. endophenotypes). The identification of risk genes and associated ADHD subtypes may eventually lead to improved diagnostic methods and treatment interventions for children with ADHD. The goal of the proposed research is to investigate electroencephalographic (EEC) measures as a biological endophenotype in ADHD and to use it in gene mapping investigations. The proposed research makes use of the ongoing UCLA ADHD Genetic Study to collect EEC data on a set of 200 affected sibling pairs (ASPs), their parents, and unaffected siblings for this investigation. The specific aims of this grant are to: 1) identify specific EEG patterns as likely endophenotypes; 2) characterize the EEG endophenotype relative to behavioral and cognitive variation associated with ADHD; and 3) test association and linkage of EEG endophenotypes in ADHD. We believe that combining behavioral, cognitive, EEG and genetic data will identify the most powerful endophentoypes for gene mapping studies in ADHD and yield important information regarding the gene-brain-behavior pathway. Innovative statistical strategies for combining these data and identifying underlying traits that are part of the genetic liability for ADHD will be used. The current study benefits greatly from this ongoing data collection because ASPs are routinely assessed using structured diagnostic interviews, neuropsychological testing, and blood draws for genotyping investigations. We are thus able to collect EEG data at a very low cost in a well characterized sample of ADHD ASPs upon which linkage studies (and candidate gene association work) are readily available.

注意缺陷多动障碍(ADHD)是一种复杂的行为障碍，影响估计的在美国，5%-10%的儿童。最近对ADHD的研究表明，这是一种复杂的行为表型是遗传异质性的结果，样本差异可能反映了不同易感基因的相对比例，它们对应的大脑相关性，以及背景基因效应。基因发现和随后的基因到大脑再到行为的阐明可能是如果降低了病原学异质性(例如，通过使用基因分离株和/或通过多重家系进行选择)，或者如果表型可以细化为家族成分，则可以与特定潜在风险基因(即内表型)更紧密地联系在一起。危险基因的识别相关的ADHD亚型最终可能导致诊断方法和治疗的改进针对ADHD儿童的干预措施。这项拟议的研究的目标是研究脑电(EEC)测量作为 ADHD的生物内表型及其在基因定位研究中的应用。拟议的研究利用加州大学洛杉矶分校正在进行的ADHD基因研究收集一组200名受影响兄弟姐妹的EEC数据配对(ASP)，他们的父母，以及未受影响的兄弟姐妹。这笔赠款的具体目的是为了：1)确定特定的脑电模式作为可能的内表型；2)表征脑电内表型与ADHD相关的行为和认知变异；以及3)测试联想和联系注意缺陷多动障碍的脑电内表型。我们认为，将行为、认知、脑电和遗传数据结合起来将为ADHD的基因图谱研究确定最强大的内分泌型，并获得重要的产量关于基因-大脑-行为途径的信息。创新的统计策略，以结合这些将使用数据和识别作为ADHD遗传易感性一部分的潜在特征。海流这项研究从正在进行的数据收集中获益良多，因为对ASP的评估通常使用有组织的诊断性访谈、神经心理测试和抽血进行基因分型调查。因此，我们能够以非常低的成本在ADHD ASP的特征良好的样本中收集EEG数据哪些连锁研究(和候选基因关联工作)是现成的。