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)
Project #
Application #
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Tyson, Frederick L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
Zip Code
Wu, Alexander C; Allen, Joseph G; Coull, Brent et al. (2018) Correlation over time of toenail metals among participants in the VA normative aging study from 1992 to 2014. J Expo Sci Environ Epidemiol :
Rodosthenous, Rodosthenis S; Kloog, Itai; Colicino, Elena et al. (2018) Extracellular vesicle-enriched microRNAs interact in the association between long-term particulate matter and blood pressure in elderly men. Environ Res 167:640-649
Aslibekyan, Stella; Agha, Golareh; Colicino, Elena et al. (2018) Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor ?. JAMA Cardiol 3:463-472
Liu, C; Marioni, R E; Hedman, Å K et al. (2018) A DNA methylation biomarker of alcohol consumption. Mol Psychiatry 23:422-433
Lepeule, Johanna; Litonjua, Augusto A; Gasparrini, Antonio et al. (2018) Lung function association with outdoor temperature and relative humidity and its interaction with air pollution in the elderly. Environ Res 165:110-117
Kresovich, Jacob K; Bulka, Catherine M; Joyce, Brian T et al. (2018) The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men. Biol Trace Elem Res 183:49-57
Joyce, Brian T; Zheng, Yinan; Zhang, Zhou et al. (2018) miRNA-Processing Gene Methylation and Cancer Risk. Cancer Epidemiol Biomarkers Prev 27:550-557
Peng, Cheng; Cayir, Akin; Sanchez-Guerra, Marco et al. (2017) Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance. Epidemiology 28:763-770
Colicino, Elena; Wilson, Ander; Frisardi, Maria Chiara et al. (2017) Telomere Length, Long-Term Black Carbon Exposure, and Cognitive Function in a Cohort of Older Men: The VA Normative Aging Study. Environ Health Perspect 125:76-81
Peng, Cheng; Sanchez-Guerra, Marco; Wilson, Ander et al. (2017) Short-term effects of air temperature and mitochondrial DNA lesions within an older population. Environ Int 103:23-29

Showing the most recent 10 out of 125 publications