Leveraging Investments in the Seychelles Child Development Study to Enable Novel Investigations of Long-Term MeHg Exposure, Toxicity Mechanisms, and Health across the Life Course

利用对塞舌尔儿童发展研究的投资，对长期甲基汞暴露、毒性机制和整个生命周期的健康进行新颖的调查

• 批准号: 10540342
• 负责人: Edwin van Wijngaarden
• 金额: $ 30.99万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-16 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540342
• 关键词: 13 year old; Address; Aging; Asthma; Attention; Autoantibodies; Autoimmune Responses; Benefits and Risks; Biochemistry; Biological; Biological Markers; Biometry; Blood Pressure; Blood specimen; Brain; Child; Child Development; Cohort Studies; Collection; Consumption; Data; Data Collection; Data Discovery; Databases; Development; Diet; Eating; Enrollment; Epidemiology; Equilibrium; Etiology; Fishes; Foundations; Funding; Future; Genes; Genetic; Glutathione; Hair; Health; Health behavior; Height; Hip region structure; Human Genetics; Hypersensitivity; Immunoglobulins; International; Investigation; Investments; Life Cycle Stages; Link; Longitudinal Studies; Mammals; Masks; Measures; Medical History; Metabolism; Methylmercury Compounds; Mothers; Neurotoxins; Northern Ireland; Nuclear; Nutrient; Nutritional Biochemistry; Oceans; Ontology; Outcome; Oxidative Stress; Participant; Persons; Phenotype; Physical Function; Physical Performance; Physical assessment; Play; Polyunsaturated Fatty Acids; Population; Population Characteristics; Predisposition; Pregnancy; Preparation; Prospective Studies; Public Health; Questionnaires; Recording of previous events; Records; Research; Resources; Risk; Risk Factors; Role; Sampling; Schools; Science; Sea; Serum; Seychelles; Source; Sweden; Symptoms; Toxic effect; Toxicology; Translational Research; Uncertainty; United States National Institutes of Health; Update; Visualization; Weight; biobank; clinically relevant; cognitive function; cognitive performance; cohort; data access; data dictionary; data harmonization; data sharing; data standards; database structure; design; developmental toxicity; fatty acid metabolism; follow-up; health determinants; immune function; improved; methylmercury exposure; novel; nutrition; prenatal; preservation; recruit; repository; sociodemographic factors; sociodemographics; statistics; stem; success; trend

For over 30 years the Seychelles Child Development Study (SCDS) has focused on examining the potential developmental risks associated with low-level methylmercury (MeHg) exposure stemming from daily ocean fish consumption during pregnancy, an issue of high public health significance. Our studies of over 3,000 participants have shown that nutrients, genetics, and maternal immune function play an important role. These findings provide important clues towards better understanding mechanisms of low-level MeHg toxicity and factors that may influence susceptibility. Our international research consortium includes four key partners with expertise in toxicology, epidemiology, biostatistics, nutritional biochemistry, and human genetics. The SCDS is a unique source of longitudinal data with extensive information on biomarkers and population characteristics. It is imperative that this resource is preserved, thoroughly documented, and enriched to realize its long-term scientific potential. The proposed study will lay the foundation for continued, integrative and translational science examining MeHg toxicity mechanisms and the long-term dynamics of low-level MeHg exposure. The current proposal has three specific aims. First, we will enrich the biorepository and outcomes database of the NC2 cohort for future studies of underlying mechanisms of MeHg toxicity and clinically-relevant phenotypes. We will re-examine 1,457 Nutrition Cohort 2 (NC2) participants who were recruited in 2008-2011 and are currently undergoing a 7-year examination. We will obtain hair and blood samples for future studies focusing on mechanisms of MeHg metabolism and toxicity. We will also collect data on medical history, sociodemographic factors, anthropometrics measures, health behaviors, and fish consumption, and we will link our study records with school examination records. Second, we will enrich the biorepository and outcome database of Main cohort study participants and their mothers to establish baseline data for novel prospective studies of MeHg toxicity across the life course. We will re-enroll the Main cohort (n=615; recruited in 1989-1990 and followed for 24 years) and their mothers (n=622, recruited in 1989-1990 and re- enrolled in 2013) and update data on health behaviors, sociodemographic factors, medical history, anthropometric measures, and fish consumption. We will collect hair and blood samples, and measure hair MeHg levels to estimate exposure across 30 years of follow up. In the Main cohort we will examine markers of autoimmune responses and correlate them with life course MeHg exposure estimates. Mothers will complete a brief assessment of physical and cognitive functioning. Finally, we will facilitate data access and sharing through improved data harmonization and discovery. We will develop an online Data Access Request and Visualization Application that will consist of a standardized data dictionary across all SCDS cohorts. It will allow users to explore our data through the visualization of descriptive statistics, and to request data and samples.

30 多年来，塞舌尔儿童发展研究 (SCDS) 一直致力于研究潜力 与日常海洋鱼类接触低水平甲基汞 (MeHg) 相关的发育风险 怀孕期间的消费是一个具有高度公共卫生意义的问题。我们的研究超过 3,000 参与者表明，营养、遗传和母体免疫功能发挥着重要作用。这些 研究结果为更好地理解低水平甲基汞毒性和机制提供了重要线索 可能影响易感性的因素。我们的国际研究联盟包括四个主要合作伙伴 毒理学、流行病学、生物统计学、营养生物化学和人类遗传学方面的专业知识。 SCDS 是 独特的纵向数据来源，包含有关生物标志物和群体特征的广泛信息。它 必须保存、彻底记录和丰富这一资源，以实现其长期目标 科学潜力。拟议的研究将为持续、综合和转化奠定基础 科学检查甲基汞毒性机制和低水平甲基汞暴露的长期动态。这 当前的提案有三个具体目标。首先，我们将丰富生物样本库和结果数据库 NC2 队列用于未来研究甲基汞毒性和临床相关的潜在机制 表型。我们将重新审查 2008-2011 年招募的 1,457 名营养队列 2 (NC2) 参与者 目前正在接受为期7年的考试。我们将获取头发和血液样本用于未来的研究 重点研究甲基汞代谢和毒性机制。我们还将收集病史数据， 社会人口统计学因素、人体测量学指标、健康行为和鱼类消费，我们将把它们联系起来 我们的学习记录和学校考试记录。二是丰富生物样本库和成果 主要队列研究参与者及其母亲的数据库，为小说建立基线数据 整个生命过程中甲基汞毒性的前瞻性研究。我们将重新注册主要队列（n=615； 1989-1990 年招募并跟踪了 24 年）及其母亲（n = 622，1989-1990 年招募并重新研究） 2013 年注册）并更新有关健康行为、社会人口因素、病史的数据， 人体测量和鱼类消费。我们将采集头发和血液样本，并测量头发 用于估计 30 年随访期间暴露程度的甲基汞水平。在主要队列中，我们将检查以下标记 自身免疫反应并将其与生命过程中甲基汞暴露估计相关联。妈妈们将完成一个 对身体和认知功能的简要评估。最后，我们将促进数据访问和共享 通过改进数据协调和发现。我们将制定在线数据访问请求并 可视化应用程序将包含跨所有 SCDS 队列的标准化数据字典。它将允许 用户通过描述性统计的可视化来探索我们的数据，并请求数据和样本。