The primary goal ofthis researcin is to evaluate the impact of prenatal exposure to polycyclic aromatic hydrocarbans (PAHs) on genome-wide epigenetic methylation patterns measured in cord blood samples of sibling-pairs. In utero exposure to PAHs, which are common traffic-related air pollutants, is an established risk factor for adverse birth outcomes, neurodevelopmental deficits, the development of childhood asthma, and markers of precancerous DNA damage. Epigenetic changes, including CpG methylation, are potential mechanisms by which environmental exposures like PAH can alter gene expression, leading to these adverse outcomes. However, it is also clear that some observed differences in methylation measured in umbilical cord blood are the result of factors other than prenatal PAH exposure. During the independent phase ofthis K99-R00 award, I propose to use the techniques I have learned during the mentored phase to explore the association between prenatal PAH exposure and epigenetic changes by comparing the methylation signature of full and half siblings. Using a paired approach, this design enables a more careful assessment ofthe impact of PAH exposure on epigenetic markers by controlling unmeasured confounding resulting from partially shared environmental, epigenetic, and genetic characteristics of siblings, which is not possible in a study of unrelated children.
The specific aims are to: 1) compare the genome-wide methylation patterns in the cord blood samples of full and half siblings using bioinformatics methods;2) evaluate the effect of prenatal PAH exposure on the epigenetic methylation signatures of sibling-pairs;3) explore the association between birth outcomes, including gestational age, birth weight, birth length, and head circumference and PAH-related epigenetic methylation patterns in sibling-pairs;4) explore whether PAH-related epigenetic methylation signatures mediate the observed relationship between prenatal PAH exposure and adverse birth outcomes in sibling-pairs;and 5) To evaluate the association between PAH-related methylation patterns measured in cord blood and three year developmental outcomes.
Prenatal exposure to PAHs has been associated with a variety of adverse postnatal health effects;these effects may be mediated by changes in DNA methylation patterns. By improving our understanding of the mechanism by which prenatal PAH exposure influences health, potentially by altering DNA methylation in cord blood, we can support claims of causation, giving more credence to policies aimed to reduce exposure.
