Epigenetic signatures in ASDs and potential relationship with environmental exposures

Background: Epigenetic mechanisms have been suggested in ASDs, particularly given the relationship of epigenetic marks to the environment and to genetic predisposition. However, there have to date been only a few studies of epigenetic marks in humans for ASD research.  There is a trade-off between limited post-mortem brain tissue versus available in-life blood samples. Further, these few studies have not integrated genetic and environmental data.

Objectives: This presentation will present the existing data for epigenetic associations with ASDs, including both brain and blood-based discovery. We will assess the relationships between brain and blood epigenetic patterns with respect to ASDs and how these relate to environmentally labile genomic regions and to genetic predisposition.

Methods: Differential methylation by ASD status was identified in post-mortem brain samples from 19 autism cases and 21 unrelated controls. Differential methylation is also identified in childhood blood samples from 292 cases and 317 controls who participated in the Study to Explore Early Development (SEED). DNA methylation signatures of ASD were compared across tissues from these independent data sets and sampling strategies. Further, available prenatal exposure (from maternal interview) and genome-wide SNP genotype data in the SEED children were examined with the methylation data to characterize the potential genetic versus environmental susceptibility at these specific epigenomic locations.

Results: Ladd-Acosta et al. found four regions of the genome to be differentially methylated between autistic cases and controls in a cohort of 41 post-mortem brain tissue samples. We will discuss the use of blood-based data for replication of these results, as well as the utility in reverse discovery, beginning with blood-based epigenetic signatures, followed by brain. We will then show how these ASD-related signatures relate to prenatal exposures and genetic predisposition.  

Conclusions: The utility of epigenetic examination of human samples to further our understanding of ASDs will depend on the ability to synthesize rare target tissue data with more abundant surrogate tissue information. This work will demonstrate this point and allow for integration and examination of the relationships between epigenetic signatures and environmental exposures. This work is funded by the CDC, Autism Speaks and NIEHS.