Genetics of EEG Patterns in ADHD

ADHD 脑电图模式的遗传学

• 批准号: 7177466
• 负责人: Sandra K Loo
• 金额: $ 33.75万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7177466
• 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; processing speed; programs; response; segregation; trait

DESCRIPTION (provided by investigator): 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.

描述（由研究者提供）：注意力缺陷多动障碍 (ADHD) 是一种复杂的行为障碍，估计影响美国 5-10% 的儿童。最近的 ADHD 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各种易感性基因的相对比例、其相应的大脑相关性和背景基因效应的变化。如果减少病因异质性（例如，通过使用遗传分离物和/或通过多重家族进行选择），或者如果表型可以细化为可能的家族成分，则可以促进基因发现和随后的基因到大脑到行为途径的阐明。与特定的潜在风险基因（即内表型）联系更紧密。风险基因和相关 ADHD 亚型的识别最终可能会改进 ADHD 儿童的诊断方法和治疗干预措施。拟议研究的目标是研究脑电图（EEC）测量作为 ADHD 的生物内表型，并将其用于基因图谱研究。拟议的研究利用正在进行的加州大学洛杉矶分校 ADHD 基因研究来收集 200 对受影响的兄弟姐妹 (ASP)、他们的父母和未受影响的兄弟姐妹的 EEC 数据，以进行本次调查。该资助的具体目标是：1）将特定的脑电图模式识别为可能的内表型； 2）描述与 ADHD 相关的行为和认知变异相关的脑电图内表型； 3）测试 ADHD 脑电图内表型的关联和联系。我们相信，结合行为、认知、脑电图和遗传数据将确定 ADHD 基因图谱研究中最强大的内表型，并产生有关基因-大脑-行为途径的重要信息。将使用创新的统计策略来结合这些数据并识别作为 ADHD 遗传倾向的一部分的潜在特征。当前的研究从持续的数据收集中受益匪浅，因为 ASP 是通过结构化诊断访谈、神经心理学测试和抽血进行基因分型研究进行常规评估的。因此，我们能够以非常低的成本在 ADHD ASP 特征良好的样本中收集脑电图数据，在此基础上可以轻松进行连锁研究（和候选基因关联工作）。