Capturing and characterizing variability of cognition and behavior in Down syndrome

项目总结/摘要 唐氏综合征（DS）是智力残疾（ID）最常见的遗传原因。尽管所有的个体 与DS具有相同的潜在病因，即21号染色体的额外拷贝，ID的严重程度可能不同 从轻度到重度，在个体之间广泛分布。具体而言，广泛的个体差异已被证明为 智商（IQ）、语言和适应行为。鉴于这些领域对学习的影响， 和日常功能，重要的是要捕捉和描述这种变异性，以指导发展， 干预措施，最大限度地提高整个生命周期的功能能力。该R 03将进行二次分析 在两个现有的数据资源，以解决两个重要方面的理解，在ID的变化， 个人DS在目标1中，我们将使用集体样本汇编多个队列中捕获的数据 561名DS儿童分析考夫曼简明智力测验2（KBIT-2）的表现， 测量智商的常用仪器。这一措施是理想的大规模研究和临床 试验，因为它只需要大约20分钟的管理。然而，由于地板效应，KBIT-2不是一个 我们的目标是描述KBIT-2的表现， 在儿童DS，以确定地板效应的程度，包括地板效应是否有较大的 对由年龄等领域定义DS儿童亚组的影响，以及 可用于DS特异性标准化评分。该目标的结果可用于指导今后的研究 研究和临床试验。在目标2中，我们将利用现有的全基因组测序数据， DS儿童，以确定DS儿童亚组之间的共享遗传变异， 认知模式和适应行为。目标2分析的结果将产生新的假设 关于与个体认知和行为变异相关的生物学途径， DS.这项建议完全符合国际海关数据库网络项目的目标。我们的目标和那些 INCLUDE项目旨在确定潜在的干预目标，以促进精准医疗 改善DS患者整个生命周期的生活质量的方法。

PROJECT SUMMARY/ABSTRACT Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). Though all individuals with DS have the same underlying etiology, an extra copy of chromosome 21, the severity of ID can vary widely, from mild to severe, across individuals. Specifically, wide individual variation has been shown for intelligence quotient (IQ), language, and adaptive behavior. Given the impact of these domains on learning and daily functioning, it is important to capture and characterize this variability to guide development of interventions that maximize functional ability across the lifespan. This R03 will perform secondary analyses on two existing data resources to address two important aspects of understanding variability in ID across individuals with DS. In Aim 1, we will compile data captured across multiple cohorts with a collective sample size of 561 children with DS to analyze performance on the Kaufman Brief Intelligence Test 2 (KBIT-2), a commonly used instrument to measure IQ. This measure is ideal for large-scale research studies and clinical trials as it only takes about 20 minutes to administer. However, due to floor effects, the KBIT-2 is not a sensitive measure of abilities in children with severe ID. We aim to characterize performance on the KBIT-2 in children with DS to determine the extent of floor effects, including whether floor effects have a bigger impact in subgroups of children with DS defined by domains such as age, as well as calculate norms that could be used for DS-specific standardize scoring. The results of this aim can be used to guide future research and clinical trials. In Aim 2, we will leverage existing whole genome sequencing data in a cohort of children with DS to identify shared genetic variation among subgroups of children with DS defined by similar patterns of cognition and adaptive behavior. The results of the Aim 2 analyses will generate new hypotheses about the biological pathways associated with variability in cognition and behavior across individuals with DS. This proposal completely aligns with the goals of the INLCUDE project. Our goals and those of the INCLUDE project are to identify potential intervention targets in order to facilitate precision medicine approaches to improve quality of life for individuals with DS across the lifespan.