Background

Based on recent evidence, more than 200 susceptibility genes have been identified to be associated with autism until now. Correspondingly, cytogenetic abnormalities have been reported for almost every chromosome. While the results of multiple genes associated with risk factors for autism are still incomplete, this paper systematically reviews published meta-analyses and systematic reviews of evidence related to autism occurrence.

Method

Literature search was conducted in the PubMed system, and the publication dates were limited between January 2000 and July 2020. We included a meta-analysis and systematic review that assessed the impact of related gene variants on the development of autism. After screening, this comprehensive literature search identified 31 meta-analyses and ten systematic reviews. We arranged the genes related to autism in the published studies according to the order of the chromosomes, and based on the results of a meta-analysis and systematic review, we selected 6 candidate genes related to ASD, namely MTHFR C677T, SLC25A12, OXTR, RELN, 5-HTTLPR, SHANK, including basic features and functions. In addition to these typical genes, we have also listed candidate genes that may exist on almost every chromosome that are related to autism.

Results

We found that the results of several literature reviews included in this study showed that the MTHFR C667T variant was a risk factor for the occurrence of ASD, and the results were consistent. The results of studies on SLC25A12 variation (rs2056202 and rs2292813) and ASD risk were inconsistent but statistically significant. No association of 5-HTTLPR was found with autism, but when subgroup analysis was performed according to ethnicity, the association was statistically significant. RELN variants (rs362691 and rs736707) were consistent with ASD risk studies, but some of the results were not statistically significant.

Conclusion

This review summarized the well-known ASD candidate genes and listed some new genes that need further study in larger sample sets to improve our understanding of the genetic basis of ASD, but sample size and heterogeneity remain major limiting factors in some genome-wide association studies. We also found that common genetic variants in some genes may be co-risk factors for autism or other neuropsychiatric disorders when we collated these results. It is worth considering screening for these mutations in clinical applications.

中文翻译：

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自闭症谱系障碍的遗传风险因素：基于系统评价和荟萃分析的系统评价

背景

根据最近的证据，到目前为止，已经确定了 200 多个易感基因与自闭症有关。相应地，几乎每条染色体都有细胞遗传学异常的报道。虽然与自闭症风险因素相关的多个基因的结果仍然不完整，但本文系统地回顾了已发表的荟萃分析和对自闭症发生相关证据的系统回顾。

方法

文献检索在 PubMed 系统中进行，出版日期限制在 2000 年 1 月至 2020 年 7 月之间。我们纳入了一项荟萃分析和系统评价，评估了相关基因变异对自闭症发展的影响。经过筛选，这项综合文献检索确定了 31 项荟萃分析和 10 项系统评价。我们将已发表研究中与自闭症相关的基因按照染色体的顺序排列，并根据荟萃分析和系统评价的结果，选择了6个与ASD相关的候选基因，即MTHFR C677T、SLC25A12、OXTR、RELN , 5-HTTLPR ,柄，包括基本特性和功能。除了这些典型基因，我们还列出了可能存在于几乎每条与自闭症相关的染色体上的候选基因。

结果

我们发现本研究纳入的多篇文献综述结果表明，MTHFR C667T变异是 ASD 发生的危险因素，结果一致。SLC25A12变异（rs2056202 和 rs2292813）和 ASD 风险的研究结果不一致，但具有统计学意义。未发现5-HTTLPR与自闭症相关，但当根据种族进行亚组分析时，该关联具有统计学意义。RELN变体（rs362691 和 rs736707）与 ASD 风险研究一致，但一些结果没有统计学意义。

结论

这篇综述总结了众所周知的 ASD 候选基因，并列出了一些需要在更大样本集中进一步研究的新基因，以提高我们对 ASD 遗传基础的理解，但样本量和异质性仍然是一些全基因组关联研究的主要限制因素. 当我们整理这些结果时，我们还发现某些基因中的常见遗传变异可能是自闭症或其他神经精神疾病的共同危险因素。值得考虑在临床应用中筛查这些突变。