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 blood 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. 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 of the first data on the ontogeny of epigenetic changes in children and their association with environmental exposures and developmental outcomes.

Public Health Relevance

Children may be susceptible to adverse effects of environmental exposures depending on their genetic make-up and expression of key enzymes. Epigenetic markers, including DNA methylation, play an important role in disease and development. The associations between methylation in children and early life exposures, sex, age, and onset of puberty are unknown. This information from minority children is imperative for completing the Human Epigenome Project and informing policy decisions to protect children's health.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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University of California Berkeley
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Huen, Karen; Calafat, Antonia M; Bradman, Asa et al. (2016) Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children. Environ Res 148:55-62
Raanan, Rachel; Balmes, John R; Harley, Kim G et al. (2016) Decreased lung function in 7-year-old children with early-life organophosphate exposure. Thorax 71:148-53
Huen, Karen; Harley, Kim; Kogut, Katherine et al. (2016) DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatr Res 79:855-62
Stein, Lauren J; Gunier, Robert B; Harley, Kim et al. (2016) Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort. Neurotoxicology 56:180-187
Rowe, Christopher; Gunier, Robert; Bradman, Asa et al. (2016) Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children. Environ Res 150:128-37
Davé, Veronica; Street, Kelly; Francis, Stephen et al. (2016) Bacterial microbiome of breast milk and child saliva from low-income Mexican-American women and children. Pediatr Res 79:846-54
Waters, Sara F; Boyce, W Thomas; Eskenazi, Brenda et al. (2016) The impact of maternal depression and overcrowded housing on associations between autonomic nervous system reactivity and externalizing behavior problems in vulnerable Latino children. Psychophysiology 53:97-104
Mora, Ana María; Oken, Emily; Rifas-Shiman, Sheryl L et al. (2016) Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood. Environ Health Perspect :
Lizarraga, Daneida; Huen, Karen; Combs, Mary et al. (2016) miRNAs differentially expressed by next-generation sequencing in cord blood buffy coat samples of boys and girls. Epigenomics 8:1619-1635
Verner, Marc-André; Gaspar, Fraser W; Chevrier, Jonathan et al. (2015) Increasing sample size in prospective birth cohorts: back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children. Environ Sci Technol 49:3940-8

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