Capturing and characterizing variability of cognition and behavior in Down syndrome

捕捉和表征唐氏综合症认知和行为的变异性

• 批准号: 10294846
• 负责人: Jessica Ezzell Hunter
• 金额: --
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2021-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294846
• 关键词: Activities of Daily Living; Adaptive Behaviors; Address; Age; Award; Behavior; Behavioral; Biological; Candidate Disease Gene; Characteristics; Child; Chromosome 21; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Collaborations; Data; Data Analyses; Data Set; Data Sources; Databases; Development; Down Syndrome; Etiology; Floor; Funding; Future; Genes; Genetic; Genetic Variation; Genotype; Goals; Incidence; Individual; Infrastructure; Intellectual functioning disability; Intelligence; Intelligence Tests; Intelligence quotient; Intervention; Investigation; Language; Lead; Learning; Live Birth; Longevity; Measurement; Measures; Methods; Neuropsychology; Outcome; Pathway interactions; Pattern; Performance; Phenotype; Population; Quality of life; Research; Research Personnel; Sample Size; Sampling; Services; Severities; Societies; Standardization; Subgroup; Time; United States National Institutes of Health; Variant; autism spectrum disorder; candidate identification; cognitive ability; cohort; daily functioning; data resource; genetic epidemiology; genetic risk factor; genetic variant; genome sequencing; guided inquiry; improved; individual variation; instrument; precision medicine; research study; secondary analysis; severe intellectual disability; success; therapy development; tool; whole genome

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.

项目摘要/摘要 唐氏综合症（DS）是智力残疾（ID）的最常见遗传原因。虽然所有人 使用DS具有相同的基本病因，染色体21的额外副本，ID的严重程度可能会有所不同 广泛，从轻度到重度，跨个体。具体而言，已显示出广泛的个人变异 智能商（IQ），语言和自适应行为。考虑到这些领域对学习的影响 以及日常运作，捕获和表征这种可变性以指导开发的发展很重要 在整个寿命中最大化功能能力的干预措施。该R03将执行次要分析 在两个现有的数据资源上，以解决理解跨越ID的两个重要方面 患有DS的人。在AIM 1中，我们将与一个集体样本一起编译在多个队列中捕获的数据 561名DS儿童的大小，用于分析Kaufman简短智能测试2（KBIT-2）上的表现 常用的仪器来测量智商。该措施非常适合大规模研究和临床 试验只需要20分钟即可进行管理。但是，由于地板效应，KBIT-2不是 严重ID儿童的能力敏感度量。我们旨在表征KBIT-2的性能 在患有DS的儿童中以确定地板效应的程度，包括地板效应是否更大 对由年龄等领域定义的DS儿童亚组的影响，以及计算规范 可以用于DS特定标准化评分。该目标的结果可用于指导未来 研究和临床试验。在AIM 2中，我们将利用现有的整个基因组测序数据 患有DS的儿童以识别患有DS的儿童亚组之间的共享遗传变异 认知和适应性行为的模式。目标2分析的结果将产生新的假设 关于与患有认知和行为的变异性相关的生物学途径 DS。该提案完全与Inlcude项目的目标完全吻合。我们的目标以及 包括项目是确定潜在的干预目标，以促进精确医学 在整个生命周期中，为患有DS的个体改善生活质量的方法。