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Health Effects of Metals in Native American Communities: A Longitudinal Multi-omics Study

金属对美洲原住民社区健康的影响：一项纵向多组学研究

基本信息

批准号：
10707904
负责人：
Ana Navas-Acien
金额：
$ 47.36万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707904
关键词：
Address Adult Affect Area Arsenic Biological Markers Blood Cardiometabolic Disease Cardiovascular Diseases Childhood Clinical Data Communities Congresses DNA Methylation Data Diabetes Mellitus Dietary Intervention Disease Epigenetic Process Ethnic Population Etiology Excision Exposure to Family Family Study Fingerprint Funding General Population Genotype Health Heart Individual Intervention Isotopes Joints Link Machine Learning Measures Mediation Metal exposure Metals Modification Molecular Monitor Mothers Multiomic Data Mus National Heart, Lung, and Blood Institute Native Americans Nutritional status Occupational Outcome Participant Pathway interactions Pattern Phenotype Plasma Population Populations at Risk Predisposition Prevention Research Risk Assessment Risk Factors Risk Reduction Schedule Site Source Subgroup Superfund Time trend Tissues Universities Uranium Urine Visit Water Water Pollutants cardiometabolic risk cardiometabolism cohort contaminated water data integration design diabetes risk disorder risk drinking water effective intervention epidemiologic data epigenomics experience genome-wide ground water innovation metabolomics multiple omics offspring programs racial population recruit sex spatiotemporal stable isotope superfund site trend tribal community tribal lands urinary wasting

项目摘要

Summary of Project 3 Native American populations have higher rates of cardiometabolic disease, including cardiovascular disease (CVD) and diabetes, than any other racial/ethnic group in the US. In the Strong Heart Study (SHS), the most important study of CVD and its risk factors in Native American communities, we showed that long-term arsenic (As) exposure can explain part of the excess burden of cardiometabolic disease. Uranium (U) exposure is associated with CVD in occupational cohorts, but data from general populations are limited. Importantly, As and U are common contaminants in Superfund sites and tribal lands, so exposure to these contaminants could be partially responsible for increased rates of cardiometabolic disease in Native American populations. Advancing effective interventions for metal-related cardiometabolic diseases requires robust data on the lasting effects of past exposures, the joint effects of As and U, and the relevant mechanisms, including downstream molecular effects. To address these needs, we will establish the Strong Heart As/U Lifelong (SHAUL) study (n=1,300) by linking data from participants at SHS visit 1 (1989–91) with their offspring recruited during the SHS family expansion in 2001–03 (visit 4). We will leverage 30 years of data and a new visit planned for 2022–23 to address the following aims. (1) Determine the cardiometabolic effects (diabetes and CVD) of childhood and adult As and U exposures overall and by sex, region, and nutritional status. Urinary metal biomarkers are available at visits 1 (reflecting childhood exposure) and 4 (reflecting adult exposure), and will be measured at visits 5 (2006–09) and 7 (2022–23) to reconstruct lifelong exposures. Water metal data, including spatial patterns, temporal trends, and stable isotope data tracing potential sources, will be available from Projects 1 and 2. (2) Determine the longitudinal epigenetic and metabolomic effects of childhood and adult As and U exposures overall and by sex, region, and nutritional status. We will measure genome-wide DNA methylation (DNAm) at visits 4 and 5, leverage extant targeted and untargeted metabolomics from the same visits, and use a joint DNAm/metabolomic multi-omics strategy. (3) Develop a predictive multi-omics fingerprint that quantifies latent and concurrent cardiometabolic risk due to As and U exposures. We will use machine learning approaches to characterize DNAm and metabolomic profiles that identify individuals at risk of diabetes or CVD due to past or current metal exposures. We will also conduct a cross-species multi-omics comparison with Project 4’s mouse data. Cardiovascular disease, diabetes, and metal exposures are major concerns for our partnering communities in the Northern Plains. By investigating the latent and concurrent effects of As and U exposures, the SHAUL study can reveal epigenetic and metabolomic mechanisms for metal-induced health effects, identify susceptible populations, and inform risk assessment. The findings will have direct implications for the prevention and control of water contaminants and cardiometabolic diseases in affected communities, including in the Northern Plains, near Superfund sites, and near other contaminated areas in the US and globally.

项目3总结