22553
Placenta Methylation and Autism Risk in the Early Autism Risk Longitudinal Investigation (EARLI)

Friday, May 13, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
S. V. Andrews1, K. M. Bakulski1, J. Feinberg2, R. Tryggvadottir3, K. D. Hansen4, S. C. Brown5, L. A. Croen6, I. Hertz-Picciotto7, C. Ladd-Acosta8, C. J. Newschaffer9, A. P. Feinberg2 and M. D. Fallin10, (1)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)Johns Hopkins University, Baltimore, MD, (3)Johns Hopkins University, Center for Epigenetics, Baltimore, MD, (4)Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (5)Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, (6)Division of Research, Kaiser Permanente, Oakland, CA, (7)Dept of Public Health Sciences, School of Medicine, UC Davis MIND Institute, Davis, CA, (8)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (9)A.J. Drexel Autism Institute, Philadelphia, PA, (10)Wendy Klag Center for Autism and Developmental Disabilities, JHBSPH, Baltimore, MD
Background:  Epigenetic mechanisms are of increasing interest in Autism Spectrum Disorder (ASD) etiology. Previous studies have established an association of altered epigenetic marks in brain and lymphoblastoid tissues of ASD cases compared to controls, including DNA methylation (DNAm) and histone 3, lysine 9 trimethyl (H3K9me3) modifications. The placenta is an important mediator of stress and environmental exposures during the gestational period, shown to be a critical risk window for neurodevelopmental disorders, and is therefore of interest for etiologic investigations of ASD. However, to date, there have been no previous genome-wide studies of placenta DNAm and ASD.

Objectives:  We measured DNAm across the genome in placenta tissue to identify genomic regions at which DNAm differed according to autism risk as quantified by the Autism Observational Scale for Infants (AOSI) administered at 12 months.

Methods: We isolated genomic DNA from the fetal side of 133 placenta samples from the Early Autism Risk Longitudinal Investigation (EARLI), an ongoing autism-enriched pregnancy cohort which enrolls families with a previously diagnosed ASD child during a new pregnancy. Families are followed throughout the gestational period and infants are followed from birth through 36 months. Recruitment was carried out at 4 sites: Drexel University School of Public Health & Children’s Hospital of Philadelphia, University of California Davis & MIND Institute, Johns Hopkins Bloomberg School of Public Health & Kennedy Krieger Institute, and Northern California Kaiser Permanente. Sequencing libraries were prepared using the NEBNext Ultra DNA Library Prep Kit for Illumina by New England BioLabs Inc. Whole-genome bisulfite sequencing at 13x coverage used 125 base pair, paired-end reads with the Illumina HiSeq 2500.  We are currently performing alignment using Bowtie2, calculating methylation at single-nucleotide resolution, and searching for differentially methylated regions (DMRs) according to AOSI score, adjusting for ancestry and sex using the BSmooth algorithm as implemented in the R package ‘bsseq’.  

Results:  AOSI score was available on 115 of the 133 children with available placental samples (range 0-19, mean [sd] = 5.25 [3.86]). We will report at the meeting the top-ranked DMRs and explore their implicated regions for their potential functional relevance to ASD and towards placenta functionality more generally.

Conclusions:  This study comprises the largest and most comprehensive survey of the placenta methylome in the context of ASD to date. Discovered regions may help define the role of placenta methylation in ASD etiology and may support the development of a placenta-based DNAm biomarker for autism risk.

See more of: Genetics
See more of: Genetics