Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Oct 14;17(10):e94607.
doi: 10.7759/cureus.94607. eCollection 2025 Oct.

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

Nazim F Hamed  1 , Abdulrahman Mohammed Alqahtani  2 , Faisal Alshaibani  3 , Sakinah Mohammed Elsharif  1 , Sadeem Ali Saeed Alamri  4 , Ashraf Serhan  5
Affiliations
Review

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

Nazim F Hamed et al. Cureus. .

Abstract

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

Background: 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.

Materials and methods: 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).

Results: 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.

Conclusion: 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.

Keywords: autism spectrum disorder; consanguinity; environmental risk factors; genetic risk factors; saudi arabia; systematic review.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. A PRISMA flowchart outlining the study selection process for the systematic review.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
See this image and copyright information in PMC

References

    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Vol. 5. Washington, D.C.: American Psychiatric Association; 2013. *Diagnostic and Statistical Manual of Mental Disorders (DSM-5)*; p. 2013.
    1. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. Maenner MJ, Warren Z, Williams AR, et al. MMWR Surveill Summ. 2023;72:1–14. - PMC - PubMed
    1. The familial risk of autism. Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. JAMA. 2014;311:1770–1777. - PMC - PubMed
    1. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Satterstrom FK, Kosmicki JA, Wang J, et al. Cell. 2020;180:568–584. - PMC - PubMed
    1. Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S, He X, Goldberg AP, et al. Nature. 2014;515:209–215. - PMC - PubMed

LinkOut - more resources