自闭症谱系障碍的全基因组DNA甲基化图谱。

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Psychiatric Genetics Pub Date : 2022-08-01 Epub Date: 2022-03-31 DOI:10.1097/YPG.0000000000000314

Ling Sun, Xueyi Wang, Xia Wang, Xiaowei Cui, Guixia Li, Le Wang, Lan Wang, Mei Song, Lulu Yu

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引用次数: 2

摘要

目的：我们旨在鉴定自闭症谱系障碍（ASD）中的差异甲基化基因及其相关信号通路。方法：首先，从基因表达综合数据库（GEO）数据集下载脑样本（GSE131706和GSE80017）和外周血样本（GSE1 09905）中的DNA甲基化谱，随后鉴定差异甲基化基因并进行功能分析。其次，GSE109905数据集用于进一步验证甲基化状态，并测试已鉴定的差异甲基化基因诊断疾病的能力。第三，在来自独立样本的全血中进行所选择的差异甲基化基因的表达测量。最后，构建了核心差异甲基化基因的蛋白质-蛋白质相互作用（PPI）网络。结果：ASD共鉴定出74个差异甲基化基因，其中高甲基化基因38个，低甲基化基因36个。在GSE109905数据集中验证后，进一步鉴定了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类受体活性的分子功能；HLA-DRB5参与细胞粘附分子、EB病毒感染以及抗原处理和呈递的信号通路。在PPI分析中，鉴定了HLA-DQA1和HLA-DRB5、FMN2和ACTR3以及CALCOO2和BAZ2B的相互作用对。有趣的是，FMN2、BAZ2B、HLA-DRB5、CALCOO2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。结论：已鉴定的差异甲基化基因和丰富的信号通路可能与ASD有关。

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Genome-wide DNA methylation profiles of autism spectrum disorder.

Objectives: We aimed to identify differentially methylated genes and related signaling pathways in autism spectrum disorder (ASD).

Methods: 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.

Results: 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.

Conclusions: Identified differentially methylated genes and enriched signaling pathway could be associated with ASD.

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来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.