Comprehensive systematic review and meta-analysis of the association between common genetic variants and autism spectrum disorder.

Aug 21, 2023

Experts: Yulian Fang,Yaqiong Cui,Zhaoqing Yin,Mengzhu Hou,Pan Guo,Hanjie Wang,Nan Liu,Chunquan Cai,Mingbang Wang

Autism spectrum disorder (ASD) is neurodevelopmental disorder characterized by stereotyped behavior and deficits in communication and social interactions. To date, numerous studies have investigated the associations between genetic variants and ASD risk. However, the results of these published studies lack a clear consensus. In the present study, we performed a systematic review on the association between genetic variants and ASD risk. Meanwhile, we conducted a meta-analysis on available data to identify the association between the single nucleotide polymorphisms (SNPs) of candidate genes and ASD risk.
We systematically searched public databases including English and Chinese from their inception to August 1, 2022. Two independent reviewers extracted data and assessed study quality. Odds ratio and 95% confidence interval were used as effect indexes to evaluate the association between the SNPs of candidate genes and the risk of ASD. Heterogeneity was explored through subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed by using Egger’s and Begg’s tests for funnel plot asymmetry. In addition, TSA analysis were performed to confirm the study findings.
We summarized 84 SNPs of 32 candidate genes from 81 articles included in the study. Subsequently, we analyzed 16 SNPs of eight genes by calculating pooled ORs, and identified eight significant SNPs of contactin associated protein 2 (CNTNAP2), methylentetrahydrofolate reductase (MTHFR), oxytocin receptor (OXTR), and vitamin D receptor (VDR). Results showed that seven SNPs, including the CNTNAP2 rs2710102 (homozygote, heterozygote, dominant and allelic models) and rs7794745 (heterozygote and dominant models), MTHFR C677T (homozygote, heterozygote, dominant, recessive and allelic models) and A1298C (dominant and allelic models), OXTR rs2254298 (homozygote and recessive models), VDR rs731236 (homozygote, dominant, recessive and allelic models) and rs2228570 (homozygote and recessive models), were showed to be correlated with an increased ASD risk. By contrast, the VDR rs7975232 was correlated with a decreased the risk of ASD under the homozygote and allelic models.
Our study summarized research evidence on the genetic variants of ASD and provides a broad and detailed overview of ASD risk genes. The C677T and A1298C polymorphisms of MTHFR, rs2710102 and rs7794745 polymorphisms of CNTNAP2, rs2254298 polymorphism of OXTR, and rs731236 and rs2228570 polymorphisms of VDR were genetic risk factors. The rs7975232 polymorphism of VDR was a genetic protective factor for ASD. Our study provides novel clues to clinicians and healthcare decision-makers to predict ASD susceptibility.

Copyright © 2023. Published by Elsevier B.V.

Author

admin

View all posts

ABOUT THE EXPERTS

Yulian Fang,Yaqiong Cui,Zhaoqing Yin,Mengzhu Hou,Pan Guo,Hanjie Wang,Nan Liu,Chunquan Cai,Mingbang Wang

Yulian Fang

Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China.

Yaqiong Cui

Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China.

Zhaoqing Yin

Division of Pediatrics, The People’s Hospital of Dehong Autonomous Prefecture, Dehong Hospital of Kunming Medical University, Mangshi, Yunnan 678400, China.

Mengzhu Hou

Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China.

Pan Guo

Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China.

Hanjie Wang

School of Life Sciences, Tianjin University and Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, 300072, China.

Nan Liu

Marshall Laboratory of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, Guangdong, 518060, China; Institute of Environment and Health, South China Hospital, Medical School, Shenzhen, 518116, China.

Chunquan Cai

Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China. Electronic address: cqcns6@126.com.

Mingbang Wang

Marshall Laboratory of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, Guangdong, 518060, China; Microbiome Therapy Center, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, 518116, China; Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children’s Hospital of Fudan University, Shanghai 201102, China. Electronic address: Mingbang.wang.bgi@qq.com.