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

• 批准号: 10218178
• 负责人: ANNE Lang DUNLOP
• 金额: $ 36.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10218178
• 关键词: 5 year old; Affect; African American; Age; Analytical Chemistry; Biological; Birth; Blood Volume; Cells; Chemicals; Child; Child Health; Clinical; Collaborations; Complex; Coupled; Data; Data Analyses; Development; Disease; Enrollment; Environment; Environmental Exposure; Environmental Health; Epigenetic Process; Etiology; Exposure to; Follow-Up Studies; Gas Chromatography; Gene Expression Regulation; Genes; Goals; Health; Human; Infant; Infrastructure; Investigation; Knowledge; Lead; Link; Liquid Chromatography; Maintenance; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolism; Methylation; Monoclonal Antibody R24; Mononuclear; Mothers; Multiomic Data; Neurodevelopmental Deficit; Newborn Infant; Obesity; Outcome; Pathway interactions; Pediatric cohort; Performance; Pesticides; Phenols; Phenotype; Polychlorinated Biphenyls; Population; Positioning Attribute; Pregnancy; Pregnant Women; Premature Birth; Preparation; Process; Research; Resolution; Resources; Risk; Risk Factors; Sampling; Serum; Smoking; Software Tools; Stress; Time; Toddler; Toxic Environmental Substances; Toxicant exposure; Visualization; Woman; Work; adverse outcome; biopsychosocial; cohort; data infrastructure; data integration; early childhood; epigenome; epigenomics; experience; follow-up; health disparity; high dimensionality; improved; in utero; metabolome; metabolomics; microbiome; milliliter; neonatal outcome; neurodevelopment; obesity in children; organochlorine pesticide; persistent organic pollutants; phthalates; polybrominated diphenyl ether; postnatal; pre-clinical; pregnant; prenatal; programs; ranpirnase; socioeconomics; stressor; tandem mass spectrometry; tool; toxicant; urinary

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 在关键产前和幼儿期间的环境暴露会导致终生健康 结果。这些暴露健康关系的基础机制很复杂，外源性 影响内源过程（例如基因调节和 代谢），扰动代谢途径，导致不良健康结果。两种不良暴露 他们的健康后果不成比例地影响非裔美国人（AA）妇女和儿童， 强调健康差异从子宫开始，并在产后放大。在结果中 AA儿童经历不成比例的是早产，神经发育定义和肥胖 - 所有这些都是 与环境暴露有关，但由于病因复杂性而理解不足。我们的团队目前是 通过18个月的早期和产后调查早产和神经发育 对环境有毒物质和孕妇妇女队列中的生物心理社会危险因素的暴露 （R01NR014800，R01MD009064）及其婴儿（R01MD009746），并通过我们的P50儿童环境 健康中心（P50ES026071）与Emory Hercules Exposome研究中心合作（P30 ES019776）。我们还在评估2-5岁的儿童肥胖和神经发育 环境儿童健康结果（ECHO）计划（UG3OD023318）。通过这种R24机制，我们 提案：（1）继续在8-14周的妊娠中注册AA妇女，在三个时间点收集数据 怀孕，并参与正在进行的产后后续研究中交付的母子二元组，以允许 持续投资产前和幼儿期之间的关系对化学和非化学物质暴露 化学压力源和儿童健康结果（队列维持目标）； （2）评估性能 高分辨率质谱法与气相色谱（GC-HRMS）相结合，以量化持久性 有机污染物（POPS）微氧化剂血清量通过将测量的流行浓度与那些进行比较 使用同一队列中的常规靶向分析化学方法测量（资源） 基础设施 - 暴露表征目标）； （3）调整工具以启用多OMIC数据集成 全面暴露评估和生物效应数据的显示，可视化和整合 - 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） 和表达）和微生物组数据 - 以及与怀孕和出生结果的关联的分析 在我们的队列和整个队列协作中（资源基础架构 - 数据准备目标）。通过 这项工作，我们期望在化学评估围绕化学评估促进环境健康科学 混合物（重点放在流行音乐上）及其不良临床前（代谢和表观遗传）的健康效应 在我们自己的高度差异孕妇和新生儿，并支持其他人群 以及涉及使用高维多摩变数据的跨核心协作。