Investigating the Role of Epigenetic Factors in ASD

Author: Hely Patel

In 2013, a novel article titled “Epigenetic Factors and Autism Spectrum Disorders,” was published. While Autism Spectrum Disorder (ASD) is a complex neurodevelopmental and genetic disorder, the etiology of the disorder is still uncertain. Researchers wrote this article to spotlight potential causes of ASD such as differences in epigenetic dysregulation. Specifically, this article discusses the dysregulation of epigenetically modified genes such as UBE3A, GABA receptor genes, and RELN, and examines how they all may serve as contributing causes of autism.

In an attempt to distinguish the etiology of ASD and analyze the disorder’s complex polygenic factors, the researchers hypothesized that the unusual epigenetic regulation is a primary etiology of autism. Their research indicated that individuals with autism elicit notable phenotypic overlap with individuals who have the maternally inherited deletion of UBE3A, which is observed in Angelman syndrome. This loss of UBE3A, or the parent-of-origin expressed genes on 15q11–q13, generally results in symptoms including insatiable appetite, obsessiveness, temper outbursts, and apparent intellectual and social difficulties. The phenotype of this deletion also includes developmental delays, severe speech and communication impairments, progressive microcephaly, and seizures – all of which are potential symptoms of autistic behaviors.

Additionally, those with autism showed a disruption of the gamma-aminobutyric acid (GABA) receptor gene cluster, which is a crucial inhibitory neurotransmitter for the human brain. GABA receptor expression is developmentally regulated, and the researchers concluded that alterations and disruption of the GABAergic interneurons lead to seizures, anxiety, and deficits in socialization similar to ASD. The apparent overlap of behavioral patterns visible in those with autism and those who have defects in GABA receptors suggests their connectivity and encourages further investigation in this topic.

Lastly, the researchers deliberate the improper methylation of the promotor region in RELN, and how this has been noticed in individuals with autism. While the researchers do not deduce a definitive association between RELN polymorphisms and autism, they discuss the reductions in RELN protein and mRNA that was found in postmortem autistic patients. They concluded that epigenetic mechanisms like DNA methylation may have impaired the RELN signaling system, specifically after puberty. If the RELN promoter is heavily methylated after puberty, then it likely leads to the start of schizophrenia and worsening of autistic behaviors.

These findings illustrate the similarities between epigenetic dysregulation in UBE3A, GABA receptor genes, and RELN with ASD. Proper regulation of gene expression via epigenetic mechanisms is critical for normal neurodevelopment; thus, it is likely that epigenetic factors contribute to neurodevelopmental disorders that share phenotypic overlap with ASD. Studying and researching the dysfunction of epigenetic regulation may provide a better understanding of the etiology of autism, which ultimately may help researchers deduce the cause of autism.


Flashner, B. M., Russo, M. E., Boileau, J. E., Leong, D. W., & Gallicano, G. I. (2013). Epigenetic factors and autism spectrum disorders. Neuromolecular medicine, 15(2), 339–350.

31 views0 comments

Recent Posts

See All