Genetics of EEG Patterns in ADHD

注意缺陷多动障碍（ADHD）是一种复杂的行为障碍， 在美国，有5-10%的儿童。最近的研究表明，多动症是一种复杂的行为， 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，其相应的大脑相关性和背景 基因效应基因发现和随后的基因到大脑到行为途径的阐明可以是 如果病原学异质性降低（例如，通过使用遗传分离株和/或 通过多重家族选择），或者如果表型可以细化为家族成分， 与特定的潜在风险基因（即内在表型）更密切相关。风险基因的识别 和相关的ADHD亚型可能最终导致诊断方法和治疗的改进 对ADHD儿童的干预。 拟议研究的目标是调查脑电图（EEC）的措施， ADHD的生物学内表型，并将其用于基因定位研究。拟议研究 利用正在进行的加州大学洛杉矶分校多动症遗传研究，收集一组200名受影响的兄弟姐妹的EEC数据 对（ASP），他们的父母，和未受影响的兄弟姐妹进行这项调查。该补助金的具体目标是 目的：1）将特定EEG模式识别为可能的内表型; 2）表征EEG内表型 与ADHD相关的行为和认知变化;和3）测试关联和联系， ADHD的EEG内表型我们相信，结合行为、认知、脑电图和遗传数据， 为ADHD的基因定位研究确定最有力的内表型， 关于基因-大脑-行为途径的信息。创新的统计战略， 数据和识别潜在的特征，是多动症的遗传责任的一部分，将被使用。当前 这项研究从持续的数据收集中受益匪浅，因为ASP是使用 结构化的诊断访谈、神经心理学测试和用于基因分型调查的抽血。 因此，我们能够以非常低的成本在ADHD ASP的良好表征样本中收集EEG数据， 这些连锁研究（和候选基因关联工作）是容易获得的。

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.