Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project

华盛顿高地哥伦比亚老龄化项目中遗传变异和代谢组学概况的流行病学整合

• 批准号: 10661335
• 负责人: RICHARD P MAYEUX
• 金额: $ 264.61万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10661335
• 关键词: Administrative Supplement; Age; Aging; Alzheimer' s Disease; Award; Biological Markers; Biology; Chemicals; Clinical; Collaborations; Communities; Consultations; Data; Dementia; Disease; Environmental Exposure; Epidemiology; Ethnic Origin; FAIR principles; Fostering; Funding; Goals; Home; Infrastructure; Institutes; Institution; Interest Group; Laboratories; Lead; Liquid substance; Mass Spectrum Analysis; Measures; Methods; Monitor; Parents; Pathogenesis; Pilot Projects; Population; Process; Protocols documentation; Publications; Quality Control; Race; Reference Standards; Research; Research Infrastructure; Research Personnel; Research Support; Resolution; Resources; Sampling; Science; System; Testing; Time; Training; Universities; Washington; authority; base; dashboard; data sharing; follow-up; genetic variant; improved; insight; instrumentation; interest; mass spectrometer; member; metabolomics; novel; novel marker; operation; pathology imaging; programs; protocol development; recruit; remote sensing; trait

ABSTRACT The objective of Exposomics for Characterization of Environmental Drivers of AD (EXCEL AD) is to provide the research infrastructure to incorporate exposomics into AD/ADRD research. Dr. Gary Miller, the founding director of the HERCULES Exposome Research Center at Emory University, has established an Exposomics Laboratory within Columbia’s CTSA and collaborated with several members of the Columbia Alzheimer’s Disease Research Center (Mayeux, Teich, Honig, Lantigua, Stern). Together with these and other AD/ADRD investigators at Columbia, he will facilitate the incorporation of exposomics into additional AD/ADRD studies at Columbia. In addition, Dr. Miller will help develop and lead a network among national NIA-funded AD/ADRD research groups interested in exposomics that will include sharing of protocols, methods, analytical reference standards, workflows, and results with a goal of harmonizing exposome data across AD studies. We hypothesize that exposomics will help identify novel biomarkers of AD, provide insight into disease pathogenesis, and identify environmental contributors to the AD-related disparities observed in different races and ethnicities. EXCEL AD will test this hypothesis through the following aims. Aim 1. To improve capacity, throughput, and identification of exogenous and endogenous chemical features through expansion of our high- resolution mass spectrometry capabilities. As we analyze more AD samples with our combined LC/GC Orbitrap platform, we will uncover significant associations with disease traits (existing biomarkers, pathology, imaging, clinical features) that require follow-up identification and characterization of unknown peaks. This effort requires dedicated instrumentation; thus, we will acquire a state-of-the-art high-resolution mass spectrometer (Thermo IQ-X Tribrid Mass Spectrometer) to aid in the identification of AD-associated features. Aim 2. To perform pilot studies for ADRC investigators using the untargeted exposomics and metabolomics platform. There are multiple AD/ADRD studies underway at Columbia University covering a range of populations with diverse ethnicity, disease stage, and age. We will provide consultations on exposomics to the Columbia AD community and perform pilot studies. In addition, we will provide analysis for select external partners. Through this supplement, we anticipate funding six projects (3 at Columbia, 3 outside) of sufficient power to yield publication-quality results. Aim 3. To develop, optimize, and distribute workflows via an online EXCEL AD Community Dashboard among other ADRCs and AD research groups interested in incorporating exposomics into their studies. We will provide training, quality control protocols and materials, and access to exposome standards to AD/ADRD investigators outside of Columbia. The Community Dashboard will compile and curate information on ongoing AD studies that are incorporating exposomics and other measures of environmental contributors to AD, including geospatial analysis, satellite-based remote sensing, and personal monitors. This will provide an intellectual home for AD/ADRD exposomics and promote FAIR data practices.

抽象的 展览组学以表征AD的环境驱动因素（Excel AD）的目的是提供 研究基础架构将展开的杂种学纳入AD/ADRD研究。创始董事加里·米勒（Gary Miller）博士 埃默里大学（Emory University）的大力神宣传研究中心（Hercules Exposome Research Center） 在哥伦比亚的CTSA中，并与哥伦比亚阿尔茨海默氏病研究的几名成员合作 中心（Mayeux，Teich，Honig，Lantigua，Stern）。以及这些和其他广告/ADRD调查人员 哥伦比亚，他将支持将外博学纳入哥伦比亚的其他广告/ADRD研究。在 此外，米勒博士将帮助建立和领导国家NIA资助的广告/ADRD研究小组之间的网络 对将包括协议，方法，分析参考标准的分享的外汇学感兴趣， 工作流程和结果旨在在广告研究中协调示威者数据。我们假设这一点 外汇学将有助于识别AD的新型生物标志物，提供有关疾病发病机理的见解，并确定 在不同种族和种族中观察到的与广告相关差异的环境贡献者。 Excel广告 将通过以下目标检验这一假设。目标1。提高容量，吞吐量和 通过扩展我们的高位 分辨率质谱能力。当我们使用合并的LC/GC分析更多的AD样品时 Orbitrap平台，我们将发现与疾病特征（现有生物标志物，病理学， 成像，临床特征）需要对未知峰的后续鉴定和表征。这项努力 需要专用的仪器；因此，我们将获得最新的高分辨率质谱仪 （Thermo IQ-X三元质谱仪），以帮助识别与广告相关的特征。目标2 使用未靶向的外汇学和代谢组学为ADRC研究者进行试验研究 平台。哥伦比亚大学正在进行多次AD/ADRD研究，涵盖了一系列人群 潜水员种族，疾病阶段和年龄。我们将向哥伦比亚广告提供有关外汇学的咨询 社区并进行试点研究。此外，我们将为某些外部合作伙伴提供分析。通过 这种补充剂，我们预计将为六个项目提供资金（3个在哥伦比亚，3个外部），足以屈服 出版质量结果。目标3。通过在线Excel广告开发，优化和分发工作流程 社区仪表板和其他ADRC和广告研究小组有兴趣合并 开发学的研究。我们将提供培训，质量控制方案和材料，并获得 哥伦比亚以外的广告/ADRD调查人员的宣传体标准。社区仪表板将编译 以及有关正在进行的广告研究的信息 广告的环境贡献者，包括地理空间分析，基于卫星的遥感和个人 监视器。这将为AD/ADRD Exposomics提供一个知识分子，并促进公平的数据实践。