Grantee Research Project Results

Epigenetics Project

EPA Grant Number: R834513C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834513
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Epigenetics Project
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Epigenetic markers are heritable changes in phenotype or gene expression in the absence of changes in DNA sequence. DNA methylation, the most common type of epigenetic modification, plays an important role in cancer, aging, neurodevelopment, and fertility. Recently, changes in global methylation in biood DNA have been associated with environmental exposures, including exposure to persistent organic pollutants, benzene, and air pollution. Little is known about DNA methylation in children, including variations with sex or age and associations with health endpoints or environmental exposures. In this proposal, we will determine whether pre- and/or postnatal exposures to DDT/E and PBDEs, persistent endocrine-disrupting toxicants, are related to global and site-specific DNA methylation in fetal blood and blood of 9-year-old children. We will also determine whether DNA methylation is related to the timing of puberty onset. Ultimately, we aim to identify specific genetic regions where epigenetic modifications can be used as biomarkers of exposure or abnormal pubertal development. We will use the rich collection of biological samples, exposure information, and health outcome data collected by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal birth cohort of 601 women and children with demonstrated high exposure to DDT/E and PBDEs.

Expected Results:

In this cohort, we will: 1) analyze global DNA methylation in newborn children by pyrosequencing of Alu and LINE-1 repeats, and Infinium Methylation assay; 2) determine ontogenetic changes in global methylation in children at birth, 1, 5, 9, and 12 years of age; 3) determine the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global methylation; 4) determine whether global DNA methylation is associated with onset of puberty and hormonal changes; and 5) examine genome-wide site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset. The total sample size will be 250 children with blood available at birth and 9 years of age. Aims 1, 3, 4 and 5 will be comprised of 100 randomly selected children in a Discovery set and 150 children in a Replication set. Aim 2 will include a subset of 50 children with blood also at 1, 5, and 12 years of age. Epigenetic markers may be a key mechanism by which environmental exposures affect children's health. This study will provide some ofthe first data on the ontogeny of epigenetic changes in children and their association with environmental exposures and developmental outcomes.

Publications and Presentations:

Publications have been submitted on this subproject: View all 77 publications for this subproject | View all 697 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 38 journal articles for this subproject | View all 169 journal articles for this center

Supplemental Keywords:

Exposure assessment, environmental, disease, toxin, health effects, child health, biomarkers, epigenetic, DNA methylation, reproductive health, neurobehavioral health, pubertal onset, metabolic syndrome, obesity, cognition, attention, memory, motor, executive function, social cognition, infants, children, latino, farmworker, agriculture, pesticide, fungicide, PBDE, DDT, Mn, California, CA, Salinas Valley, community-based, deciduous teeth, back-extrapolation, GIS, maternal,, Health, RFA, Scientific Discipline, INTERNATIONAL COOPERATION, Health Risk Assessment, Environmental Policy, Biology, Children's Health, Biochemistry, biological markers, harmful environmental agents, pesticide exposure, agricultural community, flame retardants, neurochemical effects, PBDE, children's vulnerablity, farmworkers

Progress and Final Reports:

Main Center Abstract and Reports:

R834513 Center for Integrative Research on Childhood Leukemia and the Environment - 2015

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834513C001 CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
R834513C002 Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
R834513C003 Epigenetics Project
R834513C004 Community Outreach and Translation Core

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.