Use of Omics Technologies to Address the Links between Environmental Exposures, Epigenetics, and Risk of Pediatric Obesity in a Mexican-American Population

Author(s): Tindula, Gwen Nicole | Advisor(s): Holland, Nina; Balmes, John | Abstract: The alteration of gene expression mediated by epigenetic modifications has been proposed as a mechanism by which chemical and biological factors during gestation and childhood may influence health and adult disease onset. Changes in DNA methylation, the most commonly assessed epigenetic mechanism, have been linked to numerous exposures including diet, metals, and chemicals, such as phthalates. The majority of individuals, including pregnant women and children, have detectable levels of metabolites of phthalates, which are used in consumer products to increase flexibility of plastics and as solvents. Phthalate exposure during early life has been associated with poor birth and developmental health outcomes, which may be mediated by epigenetics. Increasing evidence in human and animal models has shown an association between exposure to phthalates and DNA methylation levels. However, there is limited research on the relationship between pregnancy phthalate exposure and imprinted gene methylation. Imprinted genes exhibit expression of one parental allele and many are involved in early growth and development. Progress in the field of metabolomics has allowed for the assessment of thousands of metabolites in biological specimens. Metabolomic levels in humans have been associated with age and obesity; however, research of the effect of metabolites, especially the diverse classes of lipid metabolites, on DNA methylation is sparse. Animal studies have identified associations between maternal fatty acid dietary supplementation and offspring DNA methylation. The relationship between maternal lipid metabolites and DNA methylation of newborns has only been examined thus far in 40 mother-child dyads from a predominantly Caucasian study population. Environmental exposures, in addition to their role in epigenetic regulation, have been shown to impact human health, such as obesity status. Despite advances in the identification of additional risk factors of obesity, the influence of maternal psychosocial factors on child obesity status and biomarkers has been poorly examined.The aims of this dissertation are to address key knowledge gaps of the relationships of early life exposures, epigenetics, and childhood obesity. The analysis benefitted from numerous samples and longitudinal data accumulated since 1998 by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study of hundreds of Mexican-American children and their mothers. The well-documented environmental exposures and the high prevalence of parental and child obesity in the CHAMACOS population make this an excellent study population to assess the role of early life exposure on epigenetic mechanisms and health. Results from the research in this dissertation can inform public health prevention strategies in the general population and more targeted approaches in Hispanic subpopulations, which are projected to comprise a greater portion of the United States population in the upcoming decades.