Etiology of Reading Disabilities and Comorbid ADHD

描述(由申请人提供)：拟议研究的主要目标是评估阅读障碍(RD)和注意力缺陷/多动障碍(ADHD)这两种最常见的儿童障碍的遗传病因。为了实现这一目标，将对来自600个家庭的1650名儿童进行广泛的心理测量测试，包括WISC-IV、阅读表现和相关认知过程的测试，以及父母和教师对ADHD的评级。在这些家庭中，两个或更多兄弟姐妹中至少有一个有阅读困难的在校史。DNA将从所有兄弟姐妹和亲生父母的血液或口腔细胞样本中分离出来，每个样本将使用一种程序进行基因分型，该程序在一次检测中提供10,000多个单核苷酸多态的基因类型。这些广泛的表型和基因数据将用于实现三个目标。首先，将对迄今为止收集到的最大的RD兄弟姐妹对样本进行基因组扫描。这一分析将试图复制先前研究中已报道的RD的数量性状基因座(QTL)的定位，并有望揭示在以前的基因组扫描中未检测到的新的QTL。其次，将使用双变量连锁分析进行第一次全基因组扫描，寻找对RD和ADHD具有多效性效应的QTL。最后，将进行探索性分析，以利用丰富的表型数据集的其他方面，包括在这个因阅读困难而被确定为兄弟姐妹的丰富样本中进行DSM-IV ADHD的单变量全基因组扫描。

DESCRIPTION (provided by applicant): The primary goal of the proposed study is to assess the genetic etiology of reading disability (RD) and comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), the two most prevalent disorders of childhood. To accomplish this goal, an extensive psychometric test battery, including the WISC-IV, tests of reading performance and related cognitive processes, and parent and teacher ratings of ADHD, will be administered to a sample of 1,650 children from 600 families in which at least one of two or more siblings has a school history of reading difficulties. DNA will be isolated from blood or buccal cell samples obtained from all siblings and both biological parents, and each sample will be genotyped using a procedure that provides genotypes for over 10,000 single-nucleotide polymorphisms in a single assay. These extensive phenotypic and genotypic data will be used to accomplish three goals. First, a genome scan will be conducted in the largest sample of sibling pairs ascertained for RD that has been collected to date. This analysis will attempt to replicate the localization of quantitative trait loci (QTLs) for RD that have been reported in previous studies, and is also expected to reveal new QTLs that have not been detected in previous genome scans. Second, bivariate linkage analyses will be employed to conduct the first genome-wide scan for QTLs with pleiotropic effects on RD and ADHD. Finally, exploratory analyses will be conducted to capitalize on other aspects of the rich phenotypic dataset, including a univariate genome-wide scan for DSM-IV ADHD in this enriched sample of siblings ascertained for reading difficulties.