Genome-wide DNA methylation analysis in families with multiple individuals diagnosed with schizophrenia and intellectual disability.

IF 3 4区医学 Q2 PSYCHIATRY

World Journal of Biological Psychiatry Pub Date : 2023-10-01 Epub Date: 2023-04-18 DOI:10.1080/15622975.2023.2198595

Shengmin Zhang, Kaiyu Shi, Nan Lyu, Yunshu Zhang, Guangming Liang, Wufang Zhang, Xijin Wang, Hong Wen, Liping Wen, Hong Ma, Jijun Wang, Xin Yu, Lili Guan

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引用次数: 1

Abstract

Objectives: Schizophrenia (SZ) and intellectual disability (ID) are both included in the continuum of neurodevelopmental disorders (NDDs). DNA methylation is known to be important in the occurrence of NDDs. The family study is conducive to eliminate the effects of relative epigenetic backgrounds, and to screen for differentially methylated positions (DMPs) and regions (DMRs) that are truly associated with NDDs.

Methods: Four monozygotic twin families were recruited, and both twin individuals suffered from NDDs (either SZ, ID, or SZ plus ID). Genome-wide methylation analysis was performed in all samples and each family. DMPs and DMRs between NDD patients and unaffected individuals were identified. Functional and pathway enrichment analyses were performed on the annotated genes.

Results: Two significant DMPs annotated to CYP2E1 were found in all samples. In Family One, 1476 DMPs mapped to 880 genes, and 162 DMRs overlapping with 153 unique genes were recognised. Our results suggested that the altered methylation levels of FYN, STAT3, RAC1, and NR4A2 were associated with the development of SZ and ID. Neurodevelopment and the immune system may participate in the occurrence of SZ and ID.

Conclusions: Our findings suggested that DNA methylation participated in the development of NDDs by affecting neurodevelopment and the immune system.

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诊断为精神分裂症和智力残疾的多个体家庭的全基因组DNA甲基化分析。

目的：精神分裂症（SZ）和智力残疾（ID）都属于神经发育障碍（NDDs）的连续体。众所周知，DNA甲基化在NDD的发生中起着重要作用。该家族研究有助于消除相对表观遗传背景的影响，并筛选真正与NDD相关的差异甲基化位置（DMP）和区域（DMR）。方法：招募四个单卵双胞胎家庭，两个双胞胎个体都患有NDD（SZ、ID或SZ加ID）。对所有样本和每个家族进行全基因组甲基化分析。确定了NDD患者和未受影响个体之间的DMP和DMRs。对注释基因进行功能和途径富集分析。结果：在所有样本中均发现两个CYP2E1注释的重要DMP。在第一家族中，1476个DMP被定位到880个基因，162个DMR与153个独特基因重叠。我们的研究结果表明，FYN、STAT3、RAC1和NR4A2甲基化水平的改变与SZ和ID的发生有关。神经发育和免疫系统可能参与SZ和D的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Biological Psychiatry 医学-精神病学

CiteScore

7.00

自引率

3.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The aim of The World Journal of Biological Psychiatry is to increase the worldwide communication of knowledge in clinical and basic research on biological psychiatry. Its target audience is thus clinical psychiatrists, educators, scientists and students interested in biological psychiatry. The composition of The World Journal of Biological Psychiatry , with its diverse categories that allow communication of a great variety of information, ensures that it is of interest to a wide range of readers. The World Journal of Biological Psychiatry is a major clinically oriented journal on biological psychiatry. The opportunity to educate (through critical review papers, treatment guidelines and consensus reports), publish original work and observations (original papers and brief reports) and to express personal opinions (Letters to the Editor) makes The World Journal of Biological Psychiatry an extremely important medium in the field of biological psychiatry all over the world.