22751
Gene-Environment Interactions in ASD: PBDE Exposures and DNA Methylation in the Early Autism Risk Longitudinal Investigation

Thursday, May 12, 2016: 1:45 PM
Hall B (Baltimore Convention Center)
K. M. Bakulski1, A. P. Feinberg2, J. Feinberg2, E. Schriver3, S. C. Brown4, L. A. Croen5, I. Hertz-Picciotto6, C. J. Newschaffer3 and M. D. Fallin7, (1)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)Johns Hopkins University, Baltimore, MD, (3)A.J. Drexel Autism Institute, Philadelphia, PA, (4)Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, (5)Division of Research, Kaiser Permanente, Oakland, CA, (6)Dept of Public Health Sciences, School of Medicine, UC Davis MIND Institute, Davis, CA, (7)Wendy Klag Center for Autism and Developmental Disabilities, JHBSPH, Baltimore, MD
Background:   The environment and genetics both contribute to the etiology of autism spectrum disorder (ASD), but few studies have investigated risks from both sources jointly.  In utero exposure to polybrominated diphenyl ethers (PBDEs) has known neurodevelopmental effects and is suggested to be an ASD risk factor.  DNA methylation plays a complex role in ASD etiology, and we tested whether epigenetic state at birth may be associated with exposure to PBDEs during pregnancy.

Objectives:   The goal of this analysis is to determine whether DNA methylation measured in cord blood mediates the association, if any, between prenatal exposure to PBDEs and risk of ASD.

Methods:   In the Early Autism Risk Longitudinal Investigation (EARLI) enriched-risk ASD pregnancy cohort,  11 PBDE congeners were measured in maternal blood samples during pregnancy.  Genome-wide DNA methylation was assessed in cord blood samples using the Illumina Infinium Humanmethylation 450k array. ASD risk was estimated at 12-months using the clinician administered Autism Observation Scale for Infants (AOSI) scale.  We tested pairwise associations between PBDE concentration and DNA methylation as well as DNA methylation and AOSI score. We will use causal inference testing to assess mediation of the potential PBDE-ASD relationship via DNA methylation.

Results:  Paired maternal PBDE, cord DNAm, and offspring AOSI were available for 201 families.  AOSI scores ranged from 0-20 (mean(SD) 5.4(4.8)).  PBDE-28 concentration ranged from 0-69.1 pg/g (mean(SD): 7.6(10.2)) and PBDE-99 concentration ranged from 0-365.1 pg/g (mean(SD): 29.9(52.0)). DNA methylation was modestly associated with specific PBDE congener concentrations and DNA methylation was also associated with AOSI score at specific locations. Results of the mediation analysis will be presented.  

Conclusions:   This is a proof-of-concept study using PBDEs as an example for testing mediation of an exposure-ASD relationship via DNA methylation.  DNA methylation represents an intersection of environmental exposures and underlying genetic architecture, and may be an effective tool for estimating gene-environment interaction in ASD risk.

See more of: Gene-Environment Interactions that Contribute to ASD
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