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

摘要 用于表征AD的环境驱动因素的暴露组学（EXCEL AD）的目的是提供 研究基础设施，将基因组学纳入AD/ADRD研究。加里米勒博士， 埃默里大学HERCULES Exposome研究中心的科学家们建立了一个Exposomics实验室， 在哥伦比亚的CTSA内，并与哥伦比亚阿尔茨海默病研究的几位成员合作 中心（Mayeux、Teich、Honig、Lantigua、Stern）。与这些和其他AD/ADRD研究人员一起， 在哥伦比亚，他将促进将药物组学纳入哥伦比亚的其他AD/ADRD研究。在 此外，米勒博士还将帮助发展和领导由国家免疫局资助的国家AD/ADRD研究小组之间的网络 对生物组学感兴趣，包括共享协议，方法，分析参考标准， 工作流程和结果，目标是协调AD研究中的麻烦数据。我们假设 基因组学将有助于识别AD的新生物标志物，提供对疾病发病机制的深入了解，并确定 在不同种族和民族中观察到的AD相关差异的环境因素。EXCEL广告 我们将通过以下目标来检验这一假设。目标1.为了提高容量、吞吐量和 通过扩展我们的高- 分辨率质谱分析能力。当我们使用我们的组合LC/GC分析更多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），其需要对未知峰进行后续识别和表征。这一努力 需要专门的仪器;因此，我们将获得最先进的高分辨率质谱仪 （Thermo IQ-X Tribrid质谱仪），以帮助识别AD相关特征。目标二。到 使用非靶向代谢组学和代谢组学为ADRC研究人员进行试点研究 平台哥伦比亚大学正在进行多项AD/ADRD研究，涵盖一系列人群 不同的种族、疾病阶段和年龄。我们将向哥伦比亚广告部提供有关经济学的咨询 社区和开展试点研究。此外，我们还将为选定的外部合作伙伴提供分析。通过 本补充，我们预计资助六个项目（3在哥伦比亚，3外）的足够的权力，以产生 出版质量的结果。目标3。通过在线EXCEL AD开发、优化和分发工作流 社区仪表板以及其他ADRC和AD研究小组有兴趣将 把基因组学融入到他们的研究中。我们将提供培训、质量控制协议和材料， 对哥伦比亚以外的AD/ADRD研究人员来说，这是一个令人烦恼的标准。社区仪表板将编译 并策划正在进行的AD研究的信息，这些研究将药物组学和其他措施结合起来， AD的环境贡献者，包括地理空间分析，基于卫星的遥感和个人 监测器这将为AD/ADRD数字经济学提供一个知识之家，并促进公平的数据实践。

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.