Genetic and Environmental Risk Factors for Autism Spectrum Disorder in Saudi Arabia: A Systematic Review

This study aimed to systematically synthesize evidence on the genetic and environmental risk factors associated with autism spectrum disorder (ASD) in the Saudi population.

ASD is a complex neurodevelopmental disorder with a strong etiological basis in genetic and environmental interactions. The high rate of consanguinity in Saudi Arabia may amplify the burden of recessive genetic variants, making the investigation of region-specific risk factors a critical public health priority.

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search across PubMed, Web of Science, Scopus, and ScienceDirect was performed to identify studies on ASD risk factors in Saudi Arabia. Two independent reviewers screened records, extracted data, and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the Newcastle-Ottawa Scale (NOS).

Thirteen studies met the inclusion criteria. Genetic analyses revealed significant risk associations with specific Y-chromosome haplotypes, NR4A2 loss-of-function variants, TBX1 copy number variations (CNVs), and MTHFR single-nucleotide polymorphisms (SNPs). Key environmental risk factors identified were prenatal phthalate exposure, maternal stress, vitamin D deficiency, and consanguinity. Several studies also implicated neuroinflammatory markers (e.g., PGE2, IFN-γ) and lipid metabolism dysregulation in the disorder's pathophysiology.

The etiology of ASD in Saudi Arabia is characterized by a complex interplay between genetic predisposition, often exacerbated by consanguinity, and prenatal environmental exposures. While these findings are consistent with global research, they highlight distinct regional patterns. Future investigations should employ larger, balanced cohorts and integrate epigenetic and prospective designs to facilitate the development of targeted preventive and therapeutic strategies.