Prenatal Air Pollution Exposure and Cord Blood DNA Methylation in the Early Autism Risk Longitudinal Investigation (EARLI)

Thursday, May 11, 2017: 12:00 PM-1:40 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
J. I. Feinberg1, K. M. Bakulski2, C. Ladd-Acosta1, S. C. Brown1, L. A. Croen3, I. Hertz-Picciotto4, C. J. Newschaffer5, A. P. Feinberg6, M. D. Fallin7 and H. E. Volk1, (1)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)University of Michigan, Ann Arbor, MI, (3)Kaiser Permanente Division of Research, Oakland, CA, (4)University of California at Davis, Davis, CA, (5)Drexel University A.J. Drexel Autism Institute, Philadelphia, PA, (6)Johns Hopkins University, Baltimore, MD, (7)Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD
Background: Several epidemiological studies have shown associations between prenatal exposure to environmental contaminants such as air pollution and an increased risk for autism spectrum disorder (ASD) and adverse neurodevelopment in children. While the underlying biological mechanisms of these exposures in relation to disease risk are not well characterized, it is possible that epigenetic mechanisms such as DNA methylation can mediate the effects of prenatal exposures on neurodevelopmental outcomes.

Objectives: Our work seeks to investigate associations between prenatal exposure to criteria air pollutants (particulate matter less than 2.5 (PM2.5) and 10 microns in diameter (PM10), nitrogen dioxide (NO2) and ozone (O3)) and DNA methylation at birth in order to identify and characterize potential biological mechanisms that might explain the observed relationships between air pollution exposure and increased ASD risk.

Methods: DNA was extracted from 175 umbilical cord blood samples from babies born in the ASD enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI), at 4 different study sites (Drexel University, University of California Davis & MIND Institute, Johns Hopkins University, and Kaiser Permanente in Northern California). Genome-wide DNA methylation was then assessed using the Illumina Infinium HumanMethylation450 bead chip array (450k). We assigned prenatal exposure to ambient levels of criteria pollutants for each pregnancy address location reported by EARLI mothers based on data collected from the Environmental Protection Agency’s AirNOW monitoring network using inverse distance weighting. We performed single-site and region-based statistical analyses to identify genomic locations showing differential methylation associated with exposures. We further examined if such differences are associated with ASD phenotype.

Results: Air pollution exposure and methylation data were available for 158 cord blood samples. We report the top-ranked differentially methylated regions and individual CpG loci and explore the potential functional implications of these genomic sites in relation to ASD risk and neurodevelopment.

Conclusions: Our work helps to describe environmental exposure biology generally and also how in utero exposure to air pollution might contribute to the etiology of ASD and neurocognitive development.

See more of: Genetics
See more of: Genetics