Blood-Brain DNA Methylation Concordance in Autism Spectrum Disorders

Background:  Epigenetic processes in the brain have been investigated for their potential implications in many neurological disorders, because of the important role of epigenetics in brain function and development. While many useful epigenetic signatures have been discovered in the brain for numerous disorders, such as Alzheimer and Parkinson diseases, and autism spectrum disorders (ASD), an obvious limitation is the inability to test for them pre-mortem. 

Objectives:  The purpose of this work is to identify the extent to which a more easily-accessible tissue, such as blood, can be used as an indicator of epigenetic signatures for ASD that have been discovered in the brain.

Methods:  Ladd-Acosta et al. found four regions of the genome to be differentially methylated between ASD cases and controls in a cohort of 41 post-mortem brain tissue samples. We will attempt to replicate these regions using methylation measurements in whole-blood derived DNA from 609 individuals, including 292 ASD cases and 317 controls, enrolled in the Study to Explore Early Development (SEED), a multisite population-based case-control study of children aged 2-5 years with ASD and a control group drawn from the general population.

Results: We will present results detailing the extent to which differentially methylated regions discovered in the brain samples are replicated in the SEED cohort.

Conclusions:  The utility of replication in this context would be to provide additional evidence for the methylation differences identified in these regions, and to inform the development of non-invasive biomarkers for both ASD and ASD-related exposures.