Decoding the genetic landscape of autism: A comprehensive review

Table 3 Comparison between the different gene-environment interaction models in the context of autism spectrum disorder

Model	Key concept	Description	Examples
Diathesis-stress model	Genetic vulnerability plus environmental stressors trigger ASD	Inherited genetic predispositions (diatheses) interact with environmental stressors to manifest ASD	Prenatal stress, maternal infections, or toxin exposure in genetically predisposed individuals lead to the development of ASD
Differential susceptibility model	Genetic variants make individuals more responsive to environmental influences, both positive and negative	Certain genetic profiles heighten sensitivity to environmental conditions, affecting ASD risk and response to interventions	Genetically susceptible children may develop ASD with prenatal toxin exposure but show improvement with enriched early learning environments
Biological sensitivity to context model	Genetic variations influence sensitivity to environmental contexts	Some individuals have heightened biological reactivity to environmental stimuli due to their genetic makeup, impacting neurodevelopment and ASD risk	Children with specific genetic profiles may have increased stress responses to environmental toxins or benefit more from supportive caregiving
Gene-environment correlation model	Genetic predispositions influence exposure to certain environments	Genetic factors shape individuals' environments, through passive, evocative, or active correlations	Parents with ASD traits create environments affecting child development (passive); a child’s social difficulties lead to isolation (evocative); a child avoids noisy places (active)
Epigenetic models	Environmental factors modify gene expression through epigenetic mechanisms	Environmental influences like nutrition, toxins, or stress-induced changes in gene expression via DNA methylation or histone modification affect neurodevelopment and ASD risk	Prenatal air pollution exposure causes DNA methylation changes in neurodevelopmental genes, influencing ASD risk
Integrative models	Combines genetic, environmental, and epigenetic factors for a holistic understanding of ASD risk	Integrates multiple frameworks, considering genetic vulnerabilities, environmental exposures, and epigenetic mechanisms in ASD development	Interaction of genetic neuroinflammation susceptibility with prenatal maternal infections leads to epigenetic changes and increased ASD risk

This table provides a comparative overview of the key concepts, descriptions, and examples of how each model explains the interaction between genetic and environmental factors in autism spectrum disorder development. ASD: Autism spectrum disorder.