Idiopathic cases of ASD are a little more complicated than the above-mentioned syndromic cases. Idiopathic cases of ASD have no known underlying cause for the disorder. Nonetheless, researchers have begun attempts to unpick the epigenetic signature unique to individuals with an idiopathic ASD diagnosis. In a recent meta-analysis of peripheral blood samples, epigenome-wide investigations pinpointed 55 differentially methylated sites that were associated with ASD. Corroborating this, an investigation with identical twin pairs identified numerous differentially methylated regions associated between people with and without an ASD diagnosis, as well as between twin pairs discordant for ASD-related traits. Not only this, but the regions found to be differentially methylated were often those housing genes associated with ASD.
And it’s not only that seems to be playing an epigenetic role in ASD. Chromatin remodeling and miRNA have been found to be implicated in ASD. Using human post-mortem samples, an international team of collaborating researchers found differential on histone H3 (specifically H3K27ac) in people with ASD. As H3K27ac is an active enhancer marker, variations in acetylation will result in differential activation of transcription of a number of genes.
Another example, demonstrated in a separate study, is the differential expression of miRNA found in ASD cases compared to controls. Eight in peripheral (outside the brain) blood serum miRNAs were found to be markedly up- or down-regulated in individuals with an ASD diagnosis. Further investigations also confirmed these miRNAs to be involved in the expression of genes important for central nervous system development. But both these studies were preliminary with small sample sizes investigation and further research is needed to confirm both the findings and potential application of the results.
As highlighted by the two major subtypes of ASD (syndromic and idiopathic), ASD is highly heterogenous. This means from person to person, different combinations of multiple casual factors may contribute to the manifestation of differing combinations/severity of symptoms. This muddies the water, so to speak, where research is concerned. Thus, one person’s epigenetic profile may be entirely different to another person’s profile – yet both may have a diagnosis of ASD. Along with genetic profiling, epigenetic profiling may provide the key to sub-grouping people with ASD for the ultimate goal of facilitating more targeted therapy strategies to help improve welling being if/when needed by the individual.
- Constantino, J. (2019). On the Nature of ‘Discordance’ in Monozygotic Twin Pairs with and without Autism–a Quantitative Trait Analysis. (2019).
- Spiers, H. et al. Methylomic trajectories across human fetal brain development. Genome Res. (2015).
- Wiśniowiecka-Kowalnik, B. & Nowakowska, B. A. Genetics and epigenetics of autism spectrum disorder—current evidence in the field. Journal of Applied Genetics (2019).
- Persico, A. M. & Bourgeron, T. Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends in Neurosciences 29, 349–358 (2006).
- Maheshwari, N., Christodoulou, J. & Percy, A. Rett syndrome. Anasthesiol. und Intensivmed. (2018).
- Andrews, S. V. et al. Case-control meta-analysis of blood DNA methylation and autism spectrum disorder. Mol. Autism (2018).
- Wong, C. C. Y. et al. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Mol. Psychiatry (2014).
- Sun, W. et al. Histone Acetylome-wide Association Study of Autism Spectrum Disorder. Cell (2016).
- Kichukova, T. M., Popov, N. T., Ivanov, I. S. & Vachev, T. I. Profiling of Circulating Serum MicroRNAs in Children with Autism Spectrum Disorder using Stem-loop qRT-PCR Assay. Folia Med. (Plovdiv). (2017).