We are proposing to renew our ongoing research in Environmental Epigenetics and expand the work to discover and validate biomarkers of exposure to air pollutants and toxic metals. We also propose to develop epigenomic biomarkers of CVD itself and to link these two findings to inform potential biological pathways via which metals and pollutants cause CVD. Our understanding of these mechanisms is currently rudimentary, and often based on high doses in animals. Methylomics offers a promising approach to identification of important pathways in humans at the exposure ranges of interest. The significance of this work lies in the development of genomic biomarkers, a novel approach which utilizes the distinct properties of DNA methylation and the highly developed technologies to measure methylomic changes across the genome due to either CVD or its root causes. Biomarkers of CVD and its risk factors such as air pollution and metals are badly needed, particularly given the aging of the US population, such markers can aid in early diagnosis and prevention of disease progression. Our experienced team of investigators includes expertise in epidemiology, epigenetics, toxicology, metals analysis, bioinformatics, statistics and exposure biology. We are uniquely positioned to use recently developed epigenomic platforms to discover the validate biomarkers of exposure in an innovative longitudinal study of environmental causes of CVD. Our approach utilizes a longitudinal cohort followed for over 48 years, with a rich archive of DNA and a database with extensive CVD phenotyping and longitudinal measures of exposure to air pollutants and toxic metals.

Public Health Relevance

This project is relevant for public health research because it will identify changes in gene specific methylation that can be used as internal biomarkers of exposure using easily accessible tissue (blood). Simultaneously, it will identify gene specific patterns of DNA methylation in easily accessible tissue that precede changes in cardiovascular intermediaries (blood pressure, inflammatory markers, etc) and precede the incidence of cardiovascular events and deaths.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Cardiovascular and Sleep Epidemiology (CASE)
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Tyson, Frederick L
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Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
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Bind, Marie-Abele; Coull, Brent; Suh, Helen et al. (2014) A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution. PLoS One 9:e96000
Lepeule, Johanna; Litonjua, Augusto A; Coull, Brent et al. (2014) Long-term effects of traffic particles on lung function decline in the elderly. Am J Respir Crit Care Med 190:542-8
Bind, Marie-Abele; Lepeule, Johanna; Zanobetti, Antonella et al. (2014) Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis. Epigenetics 9:448-58
Nguyen, J L; Schwartz, J; Dockery, D W (2014) The relationship between indoor and outdoor temperature, apparent temperature, relative humidity, and absolute humidity. Indoor Air 24:103-12
Lepeule, Johanna; Bind, Marie-Abele Catherine; Baccarelli, Andrea A et al. (2014) Epigenetic influences on associations between air pollutants and lung function in elderly men: the normative aging study. Environ Health Perspect 122:566-72
Fossati, Serena; Baccarelli, Andrea; Zanobetti, Antonella et al. (2014) Ambient particulate air pollution and microRNAs in elderly men. Epidemiology 25:68-78
Colicino, Elena; Power, Melinda C; Cox, David G et al. (2014) Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment. Environ Health 13:42
Mehta, Amar J; Kloog, Itai; Zanobetti, Antonella et al. (2014) Associations between changes in city and address specific temperature and QT interval--the VA Normative Aging Study. PLoS One 9:e106258
Bind, Marie-Abele; Zanobetti, Antonella; Gasparrini, Antonio et al. (2014) Effects of temperature and relative humidity on DNA methylation. Epidemiology 25:561-9
Sordillo, Joanne E; Lange, Nancy E; Tarantini, Letizia et al. (2013) Allergen sensitization is associated with increased DNA methylation in older men. Int Arch Allergy Immunol 161:37-43

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