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)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
2R01ES015172-05A1
Application #
8183298
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Tyson, Frederick L
Project Start
2006-09-25
Project End
2016-05-31
Budget Start
2011-09-01
Budget End
2012-05-31
Support Year
5
Fiscal Year
2011
Total Cost
$664,182
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Nwanaji-Enwerem, Jamaji C; Dai, Lingzhen; Colicino, Elena et al. (2017) Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study. Environ Int 102:57-65
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
Zhang, Haixiang; Zheng, Yinan; Yoon, Grace et al. (2017) Regularized estimation in sparse high-dimensional multivariate regression, with application to a DNA methylation study. Stat Appl Genet Mol Biol 16:159-171
Zhong, Jia; Speck, Mary; Urch, Bruce et al. (2017) Reply to Lucock et al.: Significance of interpretation and misinterpretation of a small mechanistic study. Proc Natl Acad Sci U S A 114:E3880-E3881
Barfield, Richard; Shen, Jincheng; Just, Allan C et al. (2017) Testing for the indirect effect under the null for genome-wide mediation analyses. Genet Epidemiol 41:824-833
Wallwork, Rachel S; Colicino, Elena; Zhong, Jia et al. (2017) Ambient Fine Particulate Matter, Outdoor Temperature, and Risk of Metabolic Syndrome. Am J Epidemiol 185:30-39
Lee, Kyu Ha; Tadesse, Mahlet G; Baccarelli, Andrea A et al. (2017) Multivariate Bayesian variable selection exploiting dependence structure among outcomes: Application to air pollution effects on DNA methylation. Biometrics 73:232-241
Nwanaji-Enwerem, Jamaji C; Colicino, Elena; Dai, Lingzhen et al. (2017) Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age. Environ Sci Technol 51:8185-8195
Zhong, Jia; Karlsson, Oskar; Wang, Guan et al. (2017) B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial. Proc Natl Acad Sci U S A 114:3503-3508

Showing the most recent 10 out of 110 publications