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）和共病注意力缺陷/多动障碍（ADHD）的遗传病因，这是两种最常见的儿童疾病。为了实现这一目标，将对来自600个家庭的1,650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，这些家庭中至少有两个或更多兄弟姐妹中的一个有阅读困难的学校历史。将从所有兄弟姐妹和生物学父母的血液或口腔细胞样本中分离DNA，并使用在单次测定中提供超过10，000种单核苷酸多态性基因型的程序对每份样本进行基因分型。这些广泛的表型和基因型数据将用于实现三个目标。首先，将在迄今为止收集的确定RD的最大同胞对样本中进行基因组扫描。该分析将尝试复制先前研究中报道的RD数量性状位点（QTL）的定位，并且还有望揭示先前基因组扫描中未检测到的新QTL。其次，将采用双变量连锁分析对RD和ADHD具有多效性效应的QTL进行首次全基因组扫描。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，包括在确定阅读困难的兄弟姐妹的富集样本中对DSM-IV ADHD进行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.