A Comprehensive Overview of Genetic and Environmental Influences in Autism Spectrum Disorder Etiology: Processes, Interplay, and Prospects for Future Research

Backgrounds: Autism Spectrum Disorder (ASD) is a complex and varied neurodevelopmental condition marked by challenges in social communication and the presence of restricted, repetitive behaviors. Its increasing global prevalence highlights a crucial public health need to understand its origins. Modern research has moved beyond the traditional “nature versus nurture” debate, demonstrating that ASD results from dynamic interactions between genetic susceptibility and environmental factors, which influence brain development during sensitive prenatal and early postnatal periods. This review consolidates current knowledge on genetic and environmental risks, examines biological mechanisms, and identifies directions for future research. Methods: A thorough narrative review was performed by systematically searching PubMed, Scopus, and Google Scholar for peer-reviewed articles published between ۲۰۱۰ and ۲۰۲۵. Search terms included combinations such as “autism spectrum disorder,” “etiology,” “genetics,” “environment,” “gene-environment interaction,” and “epigenetics.” Articles were chosen based on relevance, study design, and scientific impact, with emphasis on meta-analyses, large cohort studies, and experimental models. Results: The genetic basis of ASD is highly diverse, involving rare, impactful de novo mutations, inherited common variants that add to polygenic risk, and syndromic forms. Well-supported environmental risk factors include advanced parental age, maternal immune activation, prenatal exposure to teratogens like valproate, and certain pregnancy complications. Importantly, gene-environment interactions are significant, where genetic predisposition increases vulnerability to environmental factors. Epigenetic mechanisms, such as DNA methylation changes in immune and synaptic pathways, appear to be key in mediating these interactions. Conclusion: Evidence supports a “multi-hit” model, where combined genetic and environmental risks disrupt specific neurodevelopmental pathways. Key challenges include determining causality for environmental factors, defining precise timing of exposures, and integrating multi-omics data across varied populations. Future research should focus on large prospective birth cohorts with detailed phenotypic data, advanced experimental models to test interactions, and greater inclusion of diverse global populations. A deeper understanding is necessary to advance toward personalized risk assessment and prevention strategies.

کلیدواژه ها:

Autism Spectrum Disorder ، Etiology ، Genetics ، Environment ، Gene-Environment Interaction ، Epigenetics ، Neurodevelopment