Mental Health Center, The First Hospital of Hebei Medical University.
Medical Department.
Psychiatr Genet. 2022 Aug 1;32(4):131-145. doi: 10.1097/YPG.0000000000000314. Epub 2022 Mar 31.
We aimed to identify differentially methylated genes and related signaling pathways in autism spectrum disorder (ASD).
First, the DNA methylation profile in the brain samples (GSE131706 and GSE80017) and peripheral blood samples (GSE109905) was downloaded from the Gene Expression Omnibus database (GEO) dataset, followed by identification of differentially methylated genes and functional analysis. Second, the GSE109905 data set was used to further validate the methylation state and test the ability to diagnose disease of identified differentially methylated genes. Third, expression measurement of selected differentially methylated genes was performed in whole blood from an independent sample. Finally, protein-protein interaction (PPI) network of core differentially methylated genes was constructed.
Totally, 74 differentially methylated genes were identified in ASD, including 38 hypermethylated genes and 36 hypomethylated genes. 15 differentially methylated genes were further identified after validation in the GSE109905 data set. Among these, major histocompatibility complex (HLA)-DQA1 was involved in the molecular function of myosin heavy chain class II receptor activity; HLA-DRB5 was involved in the signaling pathways of cell adhesion molecules, Epstein-Barr virus infection and antigen processing and presentation. In the PPI analysis, the interaction pairs of HLA-DQA1 and HLA-DRB5, FMN2 and ACTR3, and CALCOCO2 and BAZ2B were identified. Interestingly, FMN2, BAZ2B, HLA-DRB5, CALCOCO2 and DUSP22 had a potential diagnostic value for patients with ASD. The expression result of four differentially methylated genes (HLA-DRB5, NTM, IL16 and COL5A3) in the independent sample was consistent with the integrated analysis.
Identified differentially methylated genes and enriched signaling pathway could be associated with ASD.
我们旨在鉴定自闭症谱系障碍（ASD）中差异甲基化的基因和相关信号通路。
首先，从基因表达综合数据库（GEO）数据集下载大脑样本（GSE131706 和 GSE80017）和外周血样本（GSE109905）的 DNA 甲基化图谱，随后鉴定差异甲基化基因并进行功能分析。其次，使用 GSE109905 数据集进一步验证鉴定的差异甲基化基因的甲基化状态并测试其诊断疾病的能力。第三，在独立样本的全血中进行选定差异甲基化基因的表达测量。最后，构建核心差异甲基化基因的蛋白质-蛋白质相互作用（PPI）网络。
总共在 ASD 中鉴定出 74 个差异甲基化基因，包括 38 个高甲基化基因和 36 个低甲基化基因。在 GSE109905 数据集验证后，进一步鉴定出 15 个差异甲基化基因。其中，主要组织相容性复合体（HLA）-DQA1 参与肌球蛋白重链 II 受体活性的分子功能；HLA-DRB5 参与细胞黏附分子、Epstein-Barr 病毒感染和抗原加工和呈递的信号通路。在 PPI 分析中，鉴定到 HLA-DQA1 和 HLA-DRB5、FMN2 和 ACTR3、CALCOCO2 和 BAZ2B 的相互作用对。有趣的是，FMN2、BAZ2B、HLA-DRB5、CALCOCO2 和 DUSP22 对 ASD 患者具有潜在的诊断价值。四个差异甲基化基因（HLA-DRB5、NTM、IL16 和 COL5A3）在独立样本中的表达结果与综合分析一致。
鉴定出的差异甲基化基因和富集的信号通路可能与 ASD 相关。
