Research Papers

Genetics of Autism Spectrum Disorder: An Umbrella Review of Systematic Reviews and Meta-analyses

Summary: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental condition distinguished by impairments with social interaction, communication disruption and repetitive behaviours. There have been many studies assessing the association between genetic variants and ASD risk however most of these studies had low statistical power and inconsistent conclusions. This paper is a review of all the available meta-analysis on the genetic links for ASD and an in depth overview of genes related to ASD risk. The meta-analysis has identified four genes that may confer ASD risks. This study also provides evidence that clinicians and policy makers can use to guide recommendations for treatment, prevention and research related to ASD.

Read the Complete Article >


Autism spectrum disorder (ASD) is a class of neurodevelopmental conditions with a large epidemiological and societal impact worldwide. To date, numerous studies have investigated the associations between genetic variants and ASD risk. To provide a robust synthesis of published evidence of candidate gene studies for ASD, we performed an umbrella review (UR) of meta-analyses of genetic studies for ASD (PROSPERO registration number: CRD42021221868). We systematically searched eight English and Chinese databases from inception to March 31, 2022. Reviewing of eligibility, data extraction, and quality assessment were performed by two authors. In total, 28 of 5062 retrieved articles were analyzed, which investigated a combined 41 single nucleotide polymorphisms (SNPs) of nine candidate genes. Overall, 12 significant SNPs of CNTNAP2, MTHFR, OXTR, SLC25A12, and VDR were identified, of which associations with suggestive evidence included the C677T polymorphism of MTHFR (under allelic, dominant, and heterozygote models) and the rs731236 polymorphism of VDR (under allelic and homozygote models). Associations with weak evidence included the rs2710102 polymorphism of CNTNAP2 (under allelic, homozygote, and recessive models), the rs7794745 polymorphism of CNTNAP2 (under dominant and heterozygote models), the C677T polymorphism of MTHFR (under homozygote model), and the rs731236 polymorphism of VDR (under dominant and recessive models). Our UR summarizes research evidence on the genetics of ASD and provides a broad and detailed overview of risk genes for ASD. The rs2710102 and rs7794745 polymorphisms of CNTNAP2, C677T polymorphism of MTHFR, and rs731236 polymorphism of VDR may confer ASD risks. This study will provide clinicians and healthcare decision-makers with evidence-based information about the most salient candidate genes relevant to ASD and recommendations for future treatment, prevention, and research.

Article Publication Date: 15.06.22
DOI: 10.1038/s41398-022-02009-6

Mindd Foundation