The Genetic Landscape of Autism in Iran: A Systematic Review

Delaram  Barfeh; Armita  Shahesmaeilinejad; Mahin Eslami  Shahrbabaki; Anahita  Karamooz; Fatemeh  Shekari; Azam Zare  Arashlouei

doi:10.18502/ijps.v21i1.20567

Delaram Barfeh Neuroscience Research center, Afzali Poor School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Armita Shahesmaeilinejad Institute of Clinical Epidemiology and Biometry, Würzburg University, Würzburg, Germany
Mahin Eslami Shahrbabaki Department of Psychiatry, School of Medicine, Shahid Beheshti Hospital, Kerman University of Medical Sciences, Kerman, Iran
Anahita Karamooz Department of Psychiatry, School of Medicine, Shahid Beheshti Hospital, Kerman University of Medical Sciences, Kerman, Iran
Fatemeh Shekari Shahid Beheshti Psychiatry Hospital, Kerman University of Medical Science, Kerman, Iran.
Azam Zare Arashlouei Research Committee‚ Faculty of Nursing and Midwifery‚ Shahid Sadoughi University of Medical Sciences‚ Yazd‚ Iran.

DOI: https://doi.org/10.18502/ijps.v21i1.20567

Keywords: Autism Spectrum Disorder; Gene Polymorphism; Genetics; Iran; Neurodevelopmental Disorders

Abstract

Objective: Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition involving multiple genes. This study aimed to comprehensively review the genetic landscape of ASD in the Iranian population, identifying gene variants associated with increased risk, to facilitate improved diagnosis and targeted interventions.

Method: A systematic review and meta-analysis were conducted on genetic association studies of ASD in Iran up to August 2025. Comprehensive searches were performed in PubMed, Scopus, Web of Science, and Persian databases using relevant keywords. Quality assessment was performed using the Joanna Briggs Institute critical appraisal tools. Meta-analyses were carried out using Review Manager software, assessing heterogeneity and publication bias. Protein-protein interaction networks were constructed via STRING and analyzed with Cytoscape to identify key hub genes and enriched neurodevelopmental pathways.

Results: In this study, genes RORA, MTRR, MTR, Reelin, VDR, VMAT1, ACE I/D, MOCOS, HOTAIR, ANRIL, RIT2, MMP-9, GRM7, FOXP3, and GRIN2B showed significant associations with the occurrence of autism. Findings reinforce associations between multiple gene polymorphisms, especially RORA rs4774388 and MOCOS rs594445, with the risk of ASD.

Conclusion: This systematic review and meta-analysis emphasize the multifactorial genetic contributions to ASD in the Iranian population, highlighting key risk loci and neurodevelopmental pathways. The findings underscore the importance of integrating genetic, epigenetic, and environmental factors for understanding ASD etiology and developing population-tailored diagnostic and therapeutic strategies. Future studies employing larger cohorts and multi-omics approaches are warranted to further elucidate the complex genetic architecture of ASD in diverse ethnic groups.