ECHO Consortium on Perinatal Programming of Neurodevelopment

环境与基因的相互作用、共生的环境因素、性别和生命阶段定义正常 在生命过程中的变异和不利的神经发育。从子宫开始，中枢神经系统 (CNS)与不同功能域(如注意力、记忆等)的网络组件顺序发展 在不同的时期发展。因此，毒素的影响既取决于暴露的时间，也取决于剂量。发展中的 胎儿和婴儿是最脆弱的。此外，孕妇和儿童不会接触到单一的 化学的，但复杂的化学混合物。化学与非化学之间复杂的相互作用 压力源和性行为也会影响结果。我们建议成立一个新的ECHO联盟，成员为5,000人 产前登记并预期跟踪不同种族的母亲及其子女，以更好地解决 这些复杂性。我们的UG3任务将是测量怀孕和怀孕期间的环境暴露 儿童时期决定促氧化环境因素如何影响神经发育。我们将利用 我们团队开发的方法学进展包括1)一种新的基于牙齿的生物标记物，它可以 2)基于卫星遥感的大气污染模型 可以重建；3)混合统计；以及4)数据驱动的统计 重建过去的暴露时间和剂量 过去的曝光时间和剂量 识别易受攻击的窗口的方法。西奈山财团也将是更大的国家 Echo合成队列研究化学品、营养、社会因素、生物因素对健康的影响 对这些暴露的反应，以及儿童疾病背后的基因-环境相互作用 大体上说。我们既可以实现我们的UG3目标，也可以实现ECH3的目标，因为我们的队列具有广泛的 生物库，以促进扩大暴露评估和机械研究，我们的团队拥有 在四个回声焦点领域、暴露科学和队列中的表型鉴定方面的必要专业知识 管理层。在此应用程序中，我们将建立用于协调、规划和通信的基础架构 组成我们联盟的四个群体，在更大的NIH ECHO中履行类似的职能 计划，与协调中心、ECHO数据中心、儿科研究成果 (PRO)Core、未来的基因组学核心和CHEAR Exposure Core。我们的联盟将协调 我们四个已建立的队列数据库，以实现这些目标，与来自 CHEAR网络数据中心。这项提案将经验丰富的环境健康科学家与 统计学家、社会流行病学家、压力研究人员、儿童心理学家、化学家、儿科医生、 毒物学家、遗传学家和表观遗传学家建立基础设施和科学能力，以创造高度 功能性的、最先进的纵向出生队列联盟，客观地测量人类环境 该计划旨在促进儿童健康，并与更大的NIH ECHO计划整合。

Environmental interactions with genes, co-occurring environmental factors, sex, and life stage define normal variation and adverse neurodevelopment over the life course. Beginning in utero, the central nervous system (CNS) develops sequentially with network components of distinct functional domains (e.g., attention, memory, etc.) developing at different times. Thus, toxin effects depend both on timing of exposure and dose. The developing fetus and infant are most vulnerable. Moreover, pregnant women and children are not exposed to a single chemical but to complex chemical mixtures. Complex interactions between chemical and non-chemical stressors as well as sex can also influence outcomes. We propose a new ECHO Consortium of 5,000 prenatally enrolled and prospectively followed ethnically diverse mothers and their children to better address these complexities. Our UG3 mission will be to measure environmental exposures across pregnancy and childhood to determine how pro-oxidant environmental factors affect neurodevelopment. We will leverage methodological advances developed by our team including 1) a novel tooth-based biomarker that can objectively ; 2) satellite remote sensing based air pollution models that can reconstruct ; 3) mixtures statistics; and 4) data-driven statistical reconstruct past exposure timing and dose past exposure timing and dose methods to identify vulnerable windows. The Mount Sinai Consortium will also be part of the larger national ECHO synthetic cohort to study the health impacts of chemicals, nutrition, social factors, the biological response to these exposures, and the gene-environment interactions that underlie childhood disease more broadly. We can both meet our UG3 aims and the goals of the ECHO UH3, as our cohorts have extensive biobanking to facilitate expanded exposure assessment and mechanistic studies and our team has the requisite expertise in phenotyping in the four ECHO focus areas, in exposure science, and in cohort management. In this application, we will establish the infrastructure to coordinate, plan, and communicate with the four cohorts that make up our consortium, while performing similar functions within the greater NIH ECHO program, working with the Coordinating Center, the ECHO Data Center, the Pediatric Research Outcomes (PRO) Core, the future Genomics Core, and the CHEAR Exposure Core. Our Consortium will harmonize the databases of our four established cohorts to achieve these goals in tandem with experts in data science from the CHEAR Network Data Center. This proposal links highly experienced environmental health scientists with, statisticians, social epidemiologists, stress researchers, child psychologists, chemists, pediatricians, toxicologists, geneticists, and epigeneticists to build the infrastructure and scientific capacity to create a highly functional, state of the art longitudinal birth cohort consortium that objectively measures human environments that program child health and integrates with the greater NIH ECHO program.