Searching for ADHD Susceptibility Genes

描述（由申请人提供）：注意缺陷多动障碍 多动症是一种常见的儿童期与学校有关的疾病 失败、精神病合并症和心理社会残疾。因为家庭 双胞胎研究表明，ADHD有很大的遗传成分， 研究小组现在已经开始对这种疾病进行分子遗传学研究。 与其他精神疾病不同， 自相矛盾的结果，对多动症的分子遗传学研究已经产生了一个身体， 研究表明，DRD 4、DAT、DRD 5这四个基因与该疾病的病因有关 和5 HT 1B。我们之所以选择这些基因，是因为对现存基因的荟萃分析 相关研究表明，它们介导了ADHD的易感性。他们也是 与其他神经生物学研究相关， 单胺途径在疾病病因学中的作用。虽然这四个基因 与ADHD有关，具有已知功能的易感性变体 重要性尚未确定。本提案的目标是 以确定这些变量及其影响。我们有两个主要目标：第一， 使用同胞配对和基于家庭的关联研究设计，我们将寻找 DRD 4、DAT、DRD 5和5 HT 1B基因的变体，其增加易感性 注意力缺陷多动症第二，我们将检验基因变异的假设， 易患ADHD，也预测更大的持久性和不良后果， ADHD儿童及其兄弟姐妹拟议的现有数据有 已经或正在由PI与单独的NIH收集 资金（R 01 HD 37694、R 01 HD 37999）。一项研究是同胞对连锁研究， 正在从300个同胞对家庭中收集1,200名受试者， 持续性DSM-IV ADHD先证者。第二项研究建立在两个纵向 ADHD的家庭研究这些研究将产生243个核心家庭， 进行基于家庭的关联研究。联系研究和纵向研究 家庭研究使用相同的临床数据收集协议。

DESCRIPTION (provided by the applicant): Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder of childhood associated with school failure, psychiatric co-morbidity and psychosocial disability. Because family and twin studies suggest that ADHD has a substantial genetic component, several research groups have now begun molecular genetic studies of the disorder. Unlike other psychiatric conditions, which have produced an array of conflicting results, molecular genetic research into ADHD has produced a body of work implicating four genes in the etiology of the disorder: DRD4, DAT, DRD5 and 5HTlB. We have chosen these genes, because meta-analyses of extant association studies suggest they mediate susceptibility to ADHD. They are also implicated by their relevance to other neurobiologic studies, implicating monoamine pathways in the etiology of the disorder. Although these four genes have been implicated in ADHD, susceptibility variants with known functional significance have not yet been identified. The goal of the present proposal is to identify such variants and their implications. We have two main aims: First, using sib-pair and family-based association study designs, we will search for variants of the DRD4, DAT, DRD5 and 5HTlB genes, which increase susceptibility to ADHD. Second, we will test the hypothesis that the gene variants, which predispose to ADHD, also predict greater persistence and adverse outcomes among ADHD children and their siblings. The data available for the proposed have been, or are in the process of being, collected by the PI, with separate NIH funding (R01HD37694, R01HD37999). One study is a sib-pair linkage study, which is collecting 1,200 subjects from 300 sib-pair families identified through a Persistent DSM-IV ADHD proband. The second study builds upon two longitudinal family studies of ADHD. These studies will yield 243 nuclear families suitable for family-based association studies. The linkage study and the longitudinal family studies use the same clinical data collection protocols.