Maintenance and Enhancement of the Atlanta African American Maternal-Child Cohort: Exposome Profiling via High-resolution Metabolomics and Integration of Microbiome-Metabolome-Epigenome Data

亚特兰大非裔美国母婴队列的维护和增强：通过高分辨率代谢组学和微生物组-代谢组-表观基因组数据的整合进行暴露组分析

基本信息

批准号：
10447793
负责人：
ANNE Lang DUNLOP
金额：
$ 35.87万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2024-06-30
项目状态：
已结题

项目摘要

PROJECT ABSTRACT Environmental exposures during the critical prenatal and early childhood periods can result in lifelong health consequences. Mechanisms underlying these exposure-health relationships are complex, with exogenous exposures (such as chemical toxicants) affecting endogenous processes (such as gene regulation and metabolism), which perturb metabolic pathways that lead to adverse health outcomes. Both adverse exposures and their health consequences disproportionately impact African American (AA) women and children, highlighting that health disparities begin in utero and are amplified postnatally. Among outcomes disproportionately experienced by AA children are preterm birth, neurodevelopmental deficits, and obesity – all linked to environmental exposures, yet poorly understood due to etiologic complexity. Our team is currently investigating preterm birth and neurodevelopment through 18-months in relation to pre- and postnatal exposures to environmental toxicants and biopsychosocial risk factors in cohorts of pregnant AA women (R01NR014800, R01MD009064) and their infants (R01MD009746) and via our P50 Children's Environmental Health Center (P50ES026071) in collaboration with the Emory HERCULES Exposome Research Center (P30 ES019776). We are also evaluating child obesity and neurodevelopment at 2-5 years of age under the Environmental Child Health Outcomes (ECHO) program (UG3OD023318). Through this R24 mechanism, we propose to: (1) Continue to enroll AA women at 8-14 wks' gestation, collect data at three time points during pregnancy, and engage delivered mother-child dyads in on-going postnatal follow-up studies to allow continued investigation of relationships between prenatal and early childhood exposures to chemical and non- chemical stressors and child health outcomes (Cohort Maintenance Aim); (2) Evaluate the performance of high-resolution mass spectrometry coupled with gas chromatography (GC-HRMS) for quantifying persistent organic pollutants (POPs) microliter serum volumes by comparing measured POP concentrations to those measured using conventional targeted analytic chemistry approaches in the same cohort (Resource Infrastructure – Exposure Characterization Aim); and (3) Adapt tools for multi-omic data integration to enable the display, visualization, and integration of comprehensive exposure assessment and biological effect data – to include chemical toxicant concentrations and metabolomic (KEGG pathway), epigenomic (gene methylation and expression), and microbiome data – and the analysis of associations with pregnancy and birth outcomes within our cohort and across cohort collaborations (Resource Infrastructure - Data Preparation Aim). Through this work, we expect to advance environmental health science around the assessment of chemical mixtures (with a focus on POPs) and their adverse preclinical (metabolic and epigenetic) health effects in our own high disparity population of pregnant women and newborns and to support other cohorts and cross-cohort collaborations involving the use of high-dimensional multi-omic data.

项目摘要关键的产前和幼儿时期的环境暴露可能会导致终生健康这些暴露与健康关系的机制很复杂，并且具有外源性后果。影响内源性过程（例如基因调控和代谢），扰乱代谢途径，导致不良健康结果。其健康后果对非裔美国 (AA) 妇女和儿童的影响尤为严重，强调健康差异始于子宫内，并在出生后扩大。 AA 儿童不成比例地经历过早产、神经发育缺陷和肥胖——所有这些与环境暴露有关，但由于病因复杂，我们的团队目前对此知之甚少。调查早产和 18 个月内与产前和产后相关的神经发育 AA 孕妇群体中环境毒物暴露和生物心理社会危险因素（R01NR014800、R01MD009064）及其婴儿（R01MD009746）以及通过我们的 P50 儿童环境健康中心 (P50ES026071) 与埃默里大学 HERCULES 暴露研究中心 (P30) 合作 ES019776）我们还在评估 2-5 岁儿童的肥胖和神经发育。环境儿童健康成果 (ECHO) 计划 (UG3OD023318) 通过此 R24 机制，我们。建议： (1) 继续招募妊娠 8-14 周的 AA 女性，收集妊娠期间三个时间点的数据怀孕和分娩让母子二人参与持续的产后随访研究，以便继续调查产前和儿童早期接触化学物质和非化学物质之间的关系化学压力源和儿童健康结果（队列维持目标）；(2) 评估高分辨率质谱联用气相色谱法 (GC-HRMS) 用于量化持久性通过将测得的 POP 浓度与实际值进行比较，得出有机污染物 (POP) 微升血清体积在同一队列中使用传统的靶向分析化学方法进行测量（资源基础设施 - 暴露表征目标）；以及 (3) 调整用于多组学数据集成的工具，以实现综合暴露评估和生物效应数据的显示、可视化和集成—— 包括化学毒物浓度和代谢组学（KEGG 途径）、表观基因组学（基因甲基化表达）和微生物组数据——以及与妊娠和出生结果的关联分析在我们的队列内和跨队列合作（资源基础设施 - 数据准备目标）。这项工作，我们希望围绕化学品评估推进环境健康科学混合物（重点关注持久性有机污染物）及其对临床前（代谢和表观遗传）健康的不利影响我们自己的孕妇和新生儿人口差异很大，并支持其他群体以及涉及使用高维多组学数据的跨队列合作。