Scholarlink

<p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increasing prevalence and high heritability. As a key epigenetic mechanism in brain development and function, the specific mechanisms of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification in ASD remain unknown. This study conducted bioinformatics analysis of m<sup>6</sup>A-QTL data from Yoruba lymphoblastoid cell lines and the RMVar database to identify m<sup>6</sup>A-QTL SNPs and modification genes associated with ASD. A two-stage population validation includes 1244 Chinese children with ASD and controls, followed by replication in a large European cohort consisting of 18,382 cases and 27,969 controls. The potential functions of candidate variants and target genes were examined through functional annotations. There were 2830 SNPs associated with the m<sup>6</sup>A modification levels of target genes. We further identified 91 m<sup>6</sup>A-QTL-associated ASD candidate SNPs in Chinese samples and validated 8 variants in the European cohort (<i>P</i> &lt; 0.05), including three high-confidence variants: rs10242048 (<i>P</i> <sub>combined</sub> = 8.06 × 10<sup>−3</sup>), rs2304447 (<i>P</i> <sub>combined</sub> = 5.01 × 10<sup>−3</sup>), and rs4074309 (<i>P</i> <sub>combined</sub> = 1.59 × 10<sup>−2</sup>). Functional annotations revealed that rs4074309 might potentially regulate m<sup>6</sup>A levels of <i>STAT6</i> and modulate <i>LRP1</i> expression in brain tissues, binding the transcription factor THAP1. Both <i>STAT6</i> and <i>LRP1</i> are implicated in crucial neurodevelopmental pathways, such as the JAK-STAT signaling and the tau-protein kinase regulation, respectively. Our study suggests that genetic variants in m<sup>6</sup>A modification genes may contribute to ASD susceptibility. The findings highlight the importance of m<sup>6</sup>A modification in neurodevelopmental disorders and provide insights into the epigenetic mechanisms involved in ASD.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

m6A Modification Genetic Variants Associated with Autism Spectrum Disorder Risks

  • 期刊论文

  • 发表日期：

    2026年1月1日

查看全文
  • Haoxue Wang,
  • Shuai Zhao,
  • Yanlin Chen,
  • Fang Hou,
  • Kaiheng Zhu,
  • Rundong Liu,
  • Zhen Xiang,
  • Qianhui Chen,
  • Hong Fan,
  • Mengyuan Huang,
  • Zhike Wang,
  • Jiao Zhang,
  • Tianchun Wang,
  • Xi Liang,
  • Xiaoxue Zeng,
  • Zhaohui Gong,
  • Li Li,
  • Ranran Song

摘要

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increasing prevalence and high heritability. As a key epigenetic mechanism in brain development and function, the specific mechanisms of N6-methyladenosine (m6A) modification in ASD remain unknown. This study conducted bioinformatics analysis of m6A-QTL data from Yoruba lymphoblastoid cell lines and the RMVar database to identify m6A-QTL SNPs and modification genes associated with ASD. A two-stage population validation includes 1244 Chinese children with ASD and controls, followed by replication in a large European cohort consisting of 18,382 cases and 27,969 controls. The potential functions of candidate variants and target genes were examined through functional annotations. There were 2830 SNPs associated with the m6A modification levels of target genes. We further identified 91 m6A-QTL-associated ASD candidate SNPs in Chinese samples and validated 8 variants in the European cohort (P < 0.05), including three high-confidence variants: rs10242048 (P combined = 8.06 × 10−3), rs2304447 (P combined = 5.01 × 10−3), and rs4074309 (P combined = 1.59 × 10−2). Functional annotations revealed that rs4074309 might potentially regulate m6A levels of STAT6 and modulate LRP1 expression in brain tissues, binding the transcription factor THAP1. Both STAT6 and LRP1 are implicated in crucial neurodevelopmental pathways, such as the JAK-STAT signaling and the tau-protein kinase regulation, respectively. Our study suggests that genetic variants in m6A modification genes may contribute to ASD susceptibility. The findings highlight the importance of m6A modification in neurodevelopmental disorders and provide insights into the epigenetic mechanisms involved in ASD.

Graphical Abstract