Genetics of EEG Patterns in ADHD

描述（由研究者提供）：注意缺陷多动障碍（ADHD）是一种复杂的行为障碍，在美国大约影响5-10%的儿童。最近对多动症的研究表明，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各种易感基因的相对比例、相应的大脑相关性和背景基因的影响。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），或者如果可以将表型细化为可能与特定潜在风险基因更密切相关的家族成分（即内表型），则可以促进基因发现和随后对基因从大脑到行为途径的阐明。风险基因和相关ADHD亚型的识别可能最终导致ADHD儿童的诊断方法和治疗干预措施的改进。该研究的目的是研究脑电图（EEC）测量作为ADHD的生物学内表型，并将其用于基因定位调查。这项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脑电图数据。该资助的具体目的是：1)确定可能的内表型的特定脑电图模式；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)检测ADHD患儿脑电图内表型的相关性和联动性。我们相信，结合行为、认知、脑电图和遗传数据将为多动症的基因定位研究确定最强大的内表型，并提供有关基因-脑-行为途径的重要信息。将使用创新的统计策略，将这些数据结合起来，并确定ADHD遗传责任部分的潜在特征。目前的研究很大程度上得益于这种持续的数据收集，因为asp通常通过结构化诊断访谈、神经心理测试和基因分型调查的抽血来评估。因此，我们能够以非常低的成本在特征良好的ADHD asp样本中收集EEG数据，在此基础上进行连锁研究（和候选基因关联工作）是很容易获得的。

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.