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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Transition Award (R00)
Project #
4R00ES017051-03
Application #
8193401
Study Section
Special Emphasis Panel (NSS)
Program Officer
Tyson, Frederick L
Project Start
2011-01-01
Project End
2013-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
3
Fiscal Year
2011
Total Cost
$248,749
Indirect Cost
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Cowell, Whitney J; Stapleton, Heather M; Holmes, Darrell et al. (2017) Prevalence of historical and replacement brominated flame retardant chemicals in New York City homes. Emerg Contam 3:32-39
Abid, Zaynah; Roy, Ananya; Herbstman, Julie B et al. (2014) Urinary polycyclic aromatic hydrocarbon metabolites and attention/deficit hyperactivity disorder, learning disability, and special education in U.S. children aged 6 to 15. J Environ Public Health 2014:628508
Herbstman, Julie B; Wang, Shuang; Perera, Frederica P et al. (2013) Predictors and consequences of global DNA methylation in cord blood and at three years. PLoS One 8:e72824
Perera, Frederica; Vishnevetsky, Julia; Herbstman, Julie B et al. (2012) Prenatal bisphenol a exposure and child behavior in an inner-city cohort. Environ Health Perspect 120:1190-4
Herbstman, Julie B; Tang, Deliang; Zhu, Deguang et al. (2012) Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood. Environ Health Perspect 120:733-8
Lee, Hwajin; Jaffe, Andrew E; Feinberg, Jason I et al. (2012) DNA methylation shows genome-wide association of NFIX, RAPGEF2 and MSRB3 with gestational age at birth. Int J Epidemiol 41:188-99
Tang, Wan-yee; Levin, Linda; Talaska, Glenn et al. (2012) Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-? in cord white blood cells. Environ Health Perspect 120:1195-200
Perera, Frederica; Herbstman, Julie (2011) Prenatal environmental exposures, epigenetics, and disease. Reprod Toxicol 31:363-73
Guerrero-Preston, Rafael; Herbstman, Julie; Goldman, Lynn R (2011) Epigenomic biomonitors: global DNA hypomethylation as a biodosimeter of life-long environmental exposures. Epigenomics 3:1-5