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Genetics and Epigenetics of ASD

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Neurodevelopmental Pediatrics

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Abstract

Autism spectrum disorder (ASD) is a childhood-onset, life-long neurodevelopmental disorder, which is both genetically and clinically heterogeneous. Over the past few decades, technical advances have resulted in the identification of multiple genetic, epigenetic, and environmental factors in ASD etiology. The wide use of chromosomal microarrays and next-generation sequencing technologies has led to the discovery of the contribution of rare, de novo single-nucleotide and copy-number variants, as well as somatic mosaicism, to the disorder. Thus far, around 100 genes or loci have been implicated in ASD, where no single gene or locus accounts for more than 1% of all ASD cases. These ASD risk genes converge on the following pathways: (i) mechanisms regulating gene expression (such as alternative splicing); (ii) epigenetic mechanisms (such as chromatin remodeling and DNA methylation); and (iii) synaptic and signaling development (such as altered neural circuit and GABA- and glutamate-mediated neurotransmission). In addition to implicated (epi)genetic factors, studies suggest that the environmental factors play a role in ASD. Some of these environmental factors include the maternal gestational environment, the effect of parental age, gut microbiota, and sex-specific traits. Despite the advances in our understanding of (epi)genetic and environmental influences in ASD etiology, there is still much of the unexplained etiology to be understood. Future research should focus on investigating the causality of implicated variants, integrating omics data, and understanding the shared interplay between genetic, epigenetic, and environmental risk factors in ASD etiology.

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Authors and Affiliations

  1. Genetics and Genome Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada

    Bahareh A. Mojarad, Farah Qaiser & Ryan K. C. Yuen

  2. Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Farah Qaiser & Ryan K. C. Yuen

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  1. Bahareh A. Mojarad
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  2. Farah Qaiser
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  3. Ryan K. C. Yuen
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Correspondence to Ryan K. C. Yuen .

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Editors and Affiliations

  1. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia

    David D. Eisenstat

  2. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Dan Goldowitz

  3. Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Tim F. Oberlander

  4. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Jerome Y. Yager

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Mojarad, B.A., Qaiser, F., Yuen, R.K.C. (2023). Genetics and Epigenetics of ASD. In: Eisenstat, D.D., Goldowitz, D., Oberlander, T.F., Yager, J.Y. (eds) Neurodevelopmental Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-20792-1_18

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