Lee Junghan, Ha Sungji, Ahn Jaeun, Lee Seung-Tae, Choi Jong Rak, Cheon Keun-Ah
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Severance Hospital, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Front Genet. 2021 Oct 12;12:595934. doi: 10.3389/fgene.2021.595934. eCollection 2021.
The clinical heterogeneity of autism spectrum disorder (ASD) is closely associated with the diversity of genes related to ASD pathogenesis. With their low effect size, it has been hard to define the role of common variants of genes in ASD phenotype. In this study, we reviewed genetic results and clinical scores widely used for ASD diagnosis to investigate the role of genes in ASD phenotype considering their functions in molecular pathways. Genetic data from next-generation sequencing (NGS) were collected from 94 participants with ASD. We analyzed enrichment of cellular processes and gene ontology using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We compared clinical characteristics according to genetic functional characteristics. We found 266 genes containing nonsense, frame shift, missense, and splice site mutations. Results from DAVID revealed significant enrichment for "ion channel" with an enrichment score of 8.84. Moreover, ASD participants carrying mutations in ion channel-related genes showed higher total IQ ( = 0.013) and lower repetitive, restricted behavior (RRB)-related scores ( = 0.003) and mannerism subscale of social responsiveness scale scores, compared to other participants. Individuals with variants in ion channel genes showed lower RRB scores, suggesting that ion channel genes might be relatively less associated with RRB pathogenesis. These results contribute to understanding of the role of common variants in ASD and could be important in the development of precision medicine of ASD.
自闭症谱系障碍（ASD）的临床异质性与ASD发病机制相关基因的多样性密切相关。由于其效应量较低，很难确定基因常见变异在ASD表型中的作用。在本研究中，我们回顾了广泛用于ASD诊断的基因检测结果和临床评分，以根据基因在分子途径中的功能来研究基因在ASD表型中的作用。从94名ASD参与者中收集了来自下一代测序（NGS）的基因数据。我们使用注释、可视化和综合发现数据库（DAVID）分析了细胞过程和基因本体的富集情况。我们根据基因功能特征比较了临床特征。我们发现了266个包含无义、移码、错义和平移剪接位点突变的基因。DAVID的结果显示，“离子通道”显著富集，富集分数为8.84。此外，与其他参与者相比，携带离子通道相关基因突变的ASD参与者表现出更高的总智商（P = 0.013）和更低的重复、受限行为（RRB）相关评分（P = 0.003）以及社会反应量表中举止分量表的得分。离子通道基因存在变异的个体表现出较低的RRB评分，这表明离子通道基因可能与RRB发病机制的相关性相对较小。这些结果有助于理解常见变异在ASD中的作用，并且可能对ASD精准医学的发展具有重要意义。
