Biosignatures of Executive Dysfunction in Down Syndrome

摘要 本竞争修订版将扩大R 01 HD 099150 -0的范围，R 01 HD 099150 -0是一个为期五年的项目， 唐氏综合征（DS）幼儿认知和执行功能的数据收集。的焦点 R 01 HD 099150 -0是DS中未来治疗工作的结局指标确认，拟定修订版将 提供资金，支持在进行认知评估的同时收集和分析血样。 通过血液样本采集和多组学分析补充父项目数据将利用 这组患有DS的幼儿的丰富的认知表型数据，并使其有可能 初步测试DS中执行功能障碍的模型，可以为开发新的治疗方法提供信息。 在项目期间，将从入组父R 01项目第1波的60名儿童中采集血样 3年和4年。所有儿童的实际年龄在2.5-7.99岁之间。拟议的分析将力求 在转录组、蛋白质组、代谢组中识别执行功能障碍的多组学特征， 免疫状况本竞争修订版的最终目标是识别相关的内型特征 患有不同程度的执行功能障碍这种对执行功能障碍的综合生物行为检查 在DS中是新颖的，有可能改变患有DS的幼儿的治疗科学，并促进 健康的发展成果和福祉。

Abstract This Competing Revision will expand the scope of R01HD099150-0, a five-year project that involves extensive data collection on cognition and executive function in young children with Down syndrome (DS). The focus of R01HD099150-0 is outcome measure validation for future treatment work in DS, and the proposed revision will provide funds to support the collection and analysis of blood samples concurrently with cognitive assessment. Supplementing the parent project data with blood sample collection and multi-omics analyses will leverage the wealth of cognitive phenotyping data on this cohort of young children with DS, and make it possible to preliminarily test a model of executive dysfunction in DS that can inform the development of novel treatments. Blood samples will be collected from 60 children who enroll in Wave 1 of the parent R01 project during project years 3 and 4. All children will have chronological ages between 2.5-7.99 years. Proposed analyses will seek to identify multi-omics signatures of executive dysfunction in the transcriptome, proteome, metabolome, and immune profile. The ultimate goal of this Competing Revision will be to identify endotype features associated with variable executive dysfunction in DS. This integrated biobehavioral examination of executive dysfunction in DS is novel, and has the potential to transform treatment science for young children with DS and promote healthy developmental outcomes and well-being in this population.