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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01ES015172-08
Application #
8677892
Study Section
Cardiovascular and Sleep Epidemiology Study Section (CASE)
Program Officer
Chadwick, Lisa
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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Panni, Tommaso; Mehta, Amar J; Schwartz, Joel D et al. (2016) Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983-90
Prada, Diddier; Colicino, Elena; Power, Melinda C et al. (2016) APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals. Environ Res 151:101-105
Lee, Kyu Ha; Tadesse, Mahlet G; Baccarelli, Andrea A et al. (2016) Multivariate Bayesian variable selection exploiting dependence structure among outcomes: Application to air pollution effects on DNA methylation. Biometrics :
Zhang, Haixiang; Zheng, Yinan; Zhang, Zhou et al. (2016) Estimating and testing high-dimensional mediation effects in epigenetic studies. Bioinformatics 32:3150-3154

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