儿童青少年注意缺陷多动障碍外周血全基因组DNA甲基化研究
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国家重点研发计划(2016YFC1306100);北京市医院管理中心临床医学发展专项(ZYLX202128)


Genome-wide DNA methylation in peripheral blood of children and adolescents with ADHD
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    摘要:

    目的 应用甲基化芯片技术对注意缺陷多动障碍(ADHD)患儿DNA甲基化特征进行研究, 探讨 DNA 甲基化在 ADHD 发病机制中的作用。方法 于 2018 年 10 月至 2019 年 5 月选取在首都医科大 学附属北京安定医院门诊确诊的 8 例 8~16 岁的儿童青少年 ADHD 患儿作为 ADHD 组;招募 8 名年龄、 性别与 ADHD 组匹配的健康儿童青少年作为对照组。采用 Illumina Infinium Methylation EPIC Bead Chip 芯片(850K 芯片)技术对受试者进行全基因组 DNA 甲基化检测,分析和筛选差异甲基化位点。采用 gene ontology(GO)富集分析和 pathway 分析对筛选基因进行功能分类和通路分析。结果 与对照组比较, ADHD 组共有 2 068 个 CpG 位点甲基化水平发生改变,差异有统计学意义(P< 0.05)。其中有 842 个高 甲基化位点,1 226 个低甲基化位点,对应 468 个高甲基化基因如 GPR88、ARHGEF10 等,对应 705 个低 甲基化基因如 SKI、PMP2、PRR12、EBF3、BRSK2 等。GO 富集分析显示,差异甲基化基因参与生物学过 程富集于系统发育、神经系统发育以及细胞黏附等。pathway 分析显示,差异甲基化基因与钙黏蛋白信 号通路、神经元系统、Wnt 信号通路、谷氨酸能突触等信号通路相关。结论 DNA 甲基化的异常参与了 ADHD 的发生发展,检测出的差异甲基化基因可能成为 ADHD 的生物标志物或预测因子,差异甲基化基 因相关的信号通路可能与 ADHD 的发病机制相关。

    Abstract:

    Objective To study the characteristics of DNA methylation in children with attention deficit hyperactivity disorder (ADHD) using gene chip technology, and explore the role of DNA methylation in the pathogenesis of ADHD. Methods From October 2018 to May 2019, 8 children and adolescents aged 8 to 16, who were diagnosed with ADHD in the outpatient department of Beijing Anding Hospital Affiliated to Capital Medical University were randomly selected as the ADHD group. 8 healthy children and adolescents matched with ADHD group in age and gender were recruited as the control group. The Illumina Infinium Methylation EPIC Bead Chip (850K chip) technology was used to perform genome-wide DNA methylation detection, analyze and screen differentially methylated sites. Gene ontology (GO) enrichment analysis and pathway analysis were used for functional classification and pathway analysis of screened genes. Results A total of 2 068 CpG sites were altered in the ADHD group compared to the control group, and the difference was statistically significant (P< 0.05). There were 842 hypermethylation sites, 1 226 hypomethylation sites, corresponding to 468 hypermethylation genes such as GPR88 and ARHGER10, and 705 hypomethylation genes such as SKI, PMP2, PRR12, EBF3, BRSK2, etc. GO enrichment analysis showed that differentially methylated genes were involved in biological processes such as phylogeny, neurological development, cell adhesion, etc. Pathway analysis showed that the differentially methylated genes were related to signal pathways such as cadherin signal pathway, neuronal system, Wnt signal pathway, glutamatergic synapse, etc. Conclusions Abnormal DNA methylation is involved in the occurrence and development of ADHD. The detected differential methylation genes may become biomarkers or predictors of ADHD. The signal pathways related to differential methylation genes may be related to the pathogenesis of ADHD.

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罗杰,郑毅.儿童青少年注意缺陷多动障碍外周血全基因组DNA甲基化研究[J].神经疾病与精神卫生,2022,22(9):
DOI :10.3969/j. issn.1009-6574.2022.09.005.

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  • 在线发布日期: 2022-09-21