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.

项目概要/摘要 唐氏综合症（DS）是智力障碍（ID）最常见的遗传原因。虽然所有个人 与 DS 具有相同的潜在病因，21 号染色体有一个额外的拷贝，ID 的严重程度可能有所不同 范围广泛，从轻微到严重，遍及个体。具体而言，已显示出广泛的个体差异 智商（IQ）、语言和适应性行为。考虑到这些领域对学习的影响 和日常功能，捕获和描述这种变化性以指导开发非常重要 最大限度地提高整个生命周期功能能力的干预措施。此 R03 将进行二次分析 两个现有的数据资源，以解决理解 ID 变异性的两个重要方面 DS 患者。在目标 1 中，我们将通过集体样本来编译多个队列中捕获的数据 对 561 名 DS 儿童进行了规模分析，以分析考夫曼简短智力测试 2 (KBIT-2) 的表现，该测试是一项 常用的测量智商的仪器。该措施非常适合大规模研究和临床 试验，因为只需大约 20 分钟即可进行管理。然而，由于地板效应，KBIT-2 不是一个 严重智力障碍儿童能力的敏感测量。我们的目标是表征 KBIT-2 的性能 确定患有 DS 的儿童的地板效应程度，包括地板效应是否更大 对按年龄等领域定义的 DS 儿童亚组的影响，并计算标准 可用于 DS 特定的标准化评分。这一目标的结果可用于指导未来 研究和临床试验。在目标 2 中，我们将利用一组现有的全基因组测序数据 DS 儿童，以识别 DS 儿童亚组之间共有的遗传变异，这些变异由相似的定义定义 认知和适应性行为的模式。 Aim 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途径 DS。该提案完全符合 INLCUDE 项目的目标。我们的目标和其他国家的目标 INCLUDE 项目旨在确定潜在的干预目标，以促进精准医疗 改善 DS 患者一生生活质量的方法。