Cord Blood DNA Methylation and Autism Observational Scale for Infants (AOSI) Score at 12 Months in the Early Autism Risk Longitudinal Investigation (EARLI)

Background: Both genetics and environmental exposures confer risk of autism spectrum disorders (ASD), though limited precise factors responsible for increased risk have been identified.  Epigenetic state is controlled by a combination of environmental and genetic inputs and preliminary work implicates epigenetics in ASD, but no genome-wide assessment of DNA methylation prior to disease onset has been completed. 

Objectives:   To determine the relationship between DNA methylation at birth and scores on the Autism Observational Scale for Infants (AOSI) at 12 months.

Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched birth cohort, genome-scale infant cord blood DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to AOSI score at 12 months.

Results: AOSI total scores ranged from 0-20 (mean=5.4) for 94 infants with paired AOSI and methylation data available.  Methylation data from blood cell sorted reference samples were used to estimate cord blood cell type proportions.  General linear models adjusting for sex, cell type proportion, and surrogate variables for laboratory batch were applied to identify AOSI-specific differentially methylated positions as well as bump-hunting analyses, with the same covariates, to identify for differentially methylated regions.

Conclusions: The association between infant cord blood DNA methylation with AOSI score at several genomic regions will be described.  Replication in additional populations is needed to test the utility of DNA methylation marks in predicting ASD or understanding ASD mechanisms.