Prenatal PAH exposure and genome-wide methylation in a cohort of sibling-pairs

DESCRIPTION (provided by applicant) The primary goal in submitting this NIH Pathway to Independence (PI) Award is to build upon Dr. Herbstman's training as an environmental/molecular epidemiologist to develop expertise in the incorporation of emerging technology in molecular biology for application in epidemiologic research. The mentored phase includes training in three principal areas: 1) laboratory methods in molecular biology, with a focus on the analytic assessment of genome-wide epigenetic patterns in human peripheral blood and tissue;2) methods in bioinformatics to understand and evaluate the output from genome-wide epigenetic assays;and 3) training in biostatistics to incorporate large quantities of genetic data generated from genomic microarray technologies into epidemiologic research. During this training, a pilot study will be conducted to determine the correlation of methylation patterns measured in cord blood between full and half-siblings and the persistence of this methylation pattern in blood collected at three years of age in the older siblings. The skills acquired during the mentored phase will be applied during the independent phase to evaluate the impact of prenatal environmental exposure to PAHs on genome-wide epigenetic patterns in a cohort of sibling pairs. Using a more powerful matched design, this study builds upon a well-characterized ongoing cohort study, enabling a more careful assessment of the role of environmental exposures on disease risk by quantifying shared environmental, epigenetic and genetic characteristics which is not possible in a study of unrelated children. Specifically, the investigators will determine whether DNA methylation mediates the relationship between prenatal PAH exposure and adverse birth outcomes. At the completion of this award, Dr. Herbstman will have developed into an independent scientist, with expertise in the application of innovative genomic technologies in environmental/molecular epidemiologic research. With this proficiency, the investigator will be well positioned to pursue an independent career using innovative methods to evaluate the role of prenatal environmental exposures on lifetime disease risk.