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，在美国估计影响5-10%的儿童。ADHD的最新研究表明，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基因的相对比例变化，其相应的大脑相关性和背景基因效应。如果病因异质性降低（例如，通过使用遗传分离株和/或通过多重家族进行选择）或如果表型可以细化为可能与特定潜在风险基因（即内在表型）更紧密相关的家族组分，则可以促进基因发现和随后的基因-大脑-行为途径的阐明。风险基因和相关ADHD亚型的鉴定可能最终导致ADHD儿童的诊断方法和治疗干预措施的改进。拟议研究的目标是调查脑电图（EEC）措施作为ADHD的生物内表型，并将其用于基因定位研究。拟议的研究利用正在进行的加州大学洛杉矶分校ADHD遗传研究来收集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，以进行这项调查。这项资助的具体目的是：1）确定特定的EEG模式作为可能的内在表型; 2）表征EEG内在表型相对于ADHD相关的行为和认知变化; 3）测试ADHD中EEG内在表型的关联和联系。我们相信，结合行为，认知，脑电图和遗传数据将确定最强大的内表型的基因定位研究在多动症和产生重要的信息，有关基因-大脑-行为途径。将使用创新的统计策略来结合这些数据，并确定作为ADHD遗传责任一部分的潜在特征。目前的研究从这种持续的数据收集中受益匪浅，因为ASP通常使用结构化诊断访谈，神经心理学测试和抽血进行基因分型调查进行评估。因此，我们能够以非常低的成本收集EEG数据，在ADHD ASP的良好表征样本中，可以随时进行连锁研究（和候选基因关联工作）。