Down Syndrome: A UPDB Discovery Cohort for Translating Genes, Brain and Behaviors to Treatment

唐氏综合症：将基因、大脑和行为转化为治疗的 UPDB 发现队列

基本信息

批准号：
10381289
负责人：
RACHEL HESS
金额：
$ 148.48万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10381289
关键词：
Address Administrative Supplement Affect Age Alzheimer&apos s Disease Behavior Behavioral Blood Brain Brain Diseases Brain imaging Cell Line Cells Clinical Clinical and Translational Science Awards Cognition Cognitive Cohort Studies Collaborations Colorado Computerized Medical Record Congenital Abnormality Coordination and Collaboration DNA DNA Methylation Data Data Analyses Data Coordinating Center Data Set Databases Developmental Disabilities Diagnosis Dimensions Down Syndrome Endocrine Endocrine system Family Fibroblasts Functional Magnetic Resonance Imaging Funding Future Gender Generations Genes Genetic Goals Health Hematopoietic System Human Immune Immune system Immunologic Tests Individual Institutes Intellectual functioning disability Investigation Leadership Link Longevity Magnetic Resonance Imaging Mining Mosaicism Neurologic Organoids Parents Participant Phase Phenotype Plasma Population Database Preparation Proteomics Recording of previous events Registries Request for Proposals Research Research Personnel Resolution Resources Risk Role Sampling Source Specimen Speed System Testing Therapeutic Training Translating Translations United States National Institutes of Health Utah Work autism spectrum disorder biobank brain behavior cohort congenital heart disorder cytokine data dictionary data harmonization data management data mining data portal data visualization demographics genome-wide innovation insight lymphoblastoid cell line metabolomics methylome multidimensional data multimodal data multimodality multiple omics novel phenotypic data recruit relational database stem cells tractography transcriptome transcriptomics welfare

项目摘要

ABSTRACT Down syndrome (DS) or Trisomy 21, is the major genetic cause of intellectual disabilities (ID) affecting millions worldwide. Even more striking, DS is a major risk for autistic spectrum disorder (ASD), Alzheimer’s disease (AD), congenital heart disease, and deficits of the immune, endocrine and hematopoetic systems. There are no preventatives or treatments of these deficits in DS, due in part to the need for deeply annotated and deeply phenotyped DS study and discovery cohorts. To fill this gap, the goal of this Administrative Supplement to the Utah Clinical and Translational Science Award (CTSA), under the leadership of Julie R. Korenberg, is to harmonize with and expand the NIH INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) consortium, DS-ConnectTM registry, the Data Management and Portal for INCLUDE (DAPI) Project, and the Data Coordinating Center (DCC) by completing and integrating two novel DS cohorts each with existing deep annotation, and one with deep brain phenotyping and pan-omics that will overlap the Crnic Institute’s Human Trisome Project (HTP). Enabled by this supplement, we will deliver:  Recruitment of DS-UPDB, a large cohort of 300 participants (200 DS families, 100 age and gender-matched controls) covering the entire lifespan, derived from the unique multi-generational Utah Population Database (UPDB) that includes >4000 confirmed DS diagnoses, with family data and the electronic medical record (EMR). The next phase will establish the biobank and pan-omics for this unique cohort.  Deeply annotated, portal-ready demographics, clinical and family datasets for 300 participants in DS-UPDB.  Establishment of an INCLUDE cohort and Public Gateway using the pre-existing DS Brain Discovery Cohort, a unique live cohort with multidimensional linked datasets: deeply annotated, deeply phenotyped and biobanked, with extensive pre-existing datasets (cognition, behavior, MRI, DTI, fMRI, karyotypic, DNA array, methylome, labs).  Completion of Pan-omics datasets (Transcriptomics, Proteomics, Cytokines and Metabolomics) of the DS Brain Discovery Cohort (30 DS, 37 parents, 14 controls) embedded within the larger cohort.  The first inter-cohort collaboration integrating the Immune tests with brain imaging using the Brain Discovery Cohort biobank. The results will add a future dimension to DS research collaboration by establishing a deeply annotated DS cohort enriched for co-occurring conditions, within the multigenerational UPDB, and the first DS Brain Discovery Cohort (also UPDB) deeply phenotyped for brain imaging, genes and pan-omics, as an unparalleled resource for collaborative data mining by the INCLUDE consortia, HTP, for the DS-ConnectTM registry, DAPI, and DCC. This proposal is responsive to NOT-OD-20-024, maintains the scope of the Utah parent CTSA, attracts and trains junior DS investigators, and will accelerate the speed of translation to therapeutics for DS.

抽象的唐氏综合症（DS）或三体疾病21，是影响数百万的智障遗传原因（ID）全世界。更引人注目的是，DS是加速光谱障碍（ASD），阿尔茨海默氏病的主要风险（AD），先天性心脏病，并定义免疫，内分泌和造血系统。没有 DS中这些缺陷的预防或治疗，部分原因是需要深入注释表型DS研究和发现队列。为了填补这一空白，这种行政补充的目标是在朱莉·R·科伦伯格（Julie R. Korenberg）的领导下，犹他州临床和转化科学奖（CTSA）是与NIH进行协调并扩展包括（调查整个生命周期的同时存在条件了解唐氏综合症）财团，DS-ConnectTM注册表，数据管理和门户网站包括（DAPI）项目，以及完成和整合两个小说，包括（DCC） DS都与现有的深层注释，并具有深度大脑表型和泛词的同类重叠CRNIC Institute的人类Trisome项目（HTP）。通过此补品启用，我们将交付： 招募DS-UPDB，大量的300名参与者（200 ds家庭，100岁和性别匹配控件）涵盖源自唯一多代犹他州人口数据库的整个寿命（UPDB）包括> 4000个已确认的DS诊断，以及家庭数据和电子病历（EMR）。下一阶段将为这个独特的队列建立生物库和泛媒体。 针对DS-UPDB的300名参与者，深入注释，可供门户的人口统计数据，临床和家庭数据集。 建立一个包括先前存在的DS脑发现队列的队列和公共网关，具有多维链接数据集的独特现场人群：深度注释，深层表型和生物群，具有广泛的先前数据集（认知，行为，MRI，DTI，fMRI，fMRI，核型，DNA阵列，甲基团，实验室）。 DS的Pan-omics数据集（转录组学，蛋白质组学，细胞因子和代谢组学）的完成脑发现队列（30 ds，37个父母，14个对照）嵌入了较大的队列中。 使用大脑发现，将免疫测试与脑成像整合在一起的第一次合作队列生物库。结果将通过建立深入注释的DS来为DS研究合作增加未来的维度在多代updb和第一个DS脑中，富含同时发生条件的队列 Discovery COHORT（也是UPDB）深深表现为脑成像，基因和泛词，作为无与伦比的该协作数据挖掘的资源包括Consortia，HTP，用于DS-ConnectTM注册表，DAPI，DAPI，和DCC。该提案对NOT-OD-20-024的响应有响应，维持了犹他州父母CTSA的范围吸引和训练初级DS调查人员，并将加速转化为DS治疗的速度。

项目成果

期刊论文数量（651）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Outcomes of isolated distal thrombosis managed with serial compression ultrasonography.

DOI：
10.1016/j.thromres.2021.10.004
发表时间：
2021-12
期刊：
THROMBOSIS RESEARCH
影响因子：
7.5
作者：
Brewster, Alexandra C.;Jones, Aubrey E.;Johnson, Stacy A.;Saunders, John A.;Witt, Daniel M.
通讯作者：
Witt, Daniel M.

"You Feel Very Isolated": Effects of COVID-19 Pandemic on Caregiver Social Connections.

DOI：
10.1177/23337214211060166
发表时间：
2021-01
期刊：
Gerontology & geriatric medicine
影响因子：
2.7
作者：
Bristol AA;Mata AC;Mickens M;Dassel KB;Ellington L;Scammon D;Thompson A;Towsley GL;Utz RL;Terrill AL
通讯作者：
Terrill AL

Hyperglycemia exacerbates ischemic stroke outcome independent of platelet glucose uptake.