Epigenetic Pathways Linking Environmental Exposures to Autism Spectrum Disorder Risk

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is complex and involves repetitive behaviours and impairments in social communication. Despite the involvement of many genetic loci, genetic factors are not sufficient to explain the clinical diversity of ASD. There is growing evidence that epigenetic mechanisms, such as DNA methylation, histone modification and non-coding RNAs, are dynamically involved as genes and environmental exposures interact. The paper is a synthesis of multidisciplinary literature on genetics, neurobiology, and environmental health to assess how prenatal and early-life exposures to certain factors disrupt epigenetic regulation (maternal nutrition, metabolic disorders, stress, parental age, and exposure to toxicants e.g., heavy metals, pesticides, endocrine disruptors) and cause ASD. The systematic review and synthesis conceptually assessed studies on gene-environment (GxE) interactions, transgenerational inheritance and biomarkers. It has been shown that the exposure to the environment alters the process of methylation and chromatin of neurodevelopmental genes (MECP2, OXTR, RELN), which affects brain connectivity and behavior. The GxE interactions increase the risk in genetically vulnerable individuals, and a few of these epigenetic changes are transgenerational. Placenta, cord blood and saliva epigenetic biomarkers have potential of early diagnosis. Notably, the epigenetic changes can be reversed, and this presents a possibility of nutritional, pharmacological, and behavioral intervention. ASD occurs as a result of interaction between genomic vulnerability to a particular condition and environmental influences that interact with epigenetic control. The understanding of epigenetics redefines ASD as a modifiable process and approves new strategies of prevention, precision medicine, and early intervention. The future research is needed to determine causality, enhance the validity of biomarkers and deal with ethical issues in predictive epigenetics.