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受欺凌的表观基因组学:遭受欺凌后DNA甲基化的变化

Epigenomics of being bullied: changes in DNA methylation following bullying exposure.

作者信息

Mulder Rosa H, Walton Esther, Neumann Alexander, Houtepen Lotte C, Felix Janine F, Bakermans-Kranenburg Marian J, Suderman Matthew, Tiemeier Henning, van IJzendoorn Marinus H, Relton Caroline L, Cecil Charlotte A M

机构信息

Institute of Education and Child Studies, Leiden University , Leiden, The Netherlands.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, The Netherlands.

出版信息

Epigenetics. 2020 Jun-Jul;15(6-7):750-764. doi: 10.1080/15592294.2020.1719303. Epub 2020 Jan 28.

Abstract

Bullying among children is ubiquitous and associated with pervasive mental health problems. However, little is known about the biological pathways that change after exposure to bullying. Epigenome-wide changes in DNA methylation in peripheral blood were studied from pre- to post measurement of bullying exposure, in a longitudinal study of the population-based Generation R Study and Avon Longitudinal Study of Parents and Children (combined = 1,352). Linear mixed-model results were meta-analysed to estimate how DNA methylation changed as a function of exposure to bullying. Sensitivity analyses including co-occurring child characteristics and risks were performed, as well as a Gene Ontology analysis. A candidate follow-up was employed for CpG (cytosine-phosphate-guanine) sites annotated to and . One site, cg17312179, showed small changes in DNA methylation associated to bullying exposure ( = -2.67e-03, SE = 4.97e-04, = 7.17e-08). This site is annotated to , an oncogene related to Golgi apparatus functioning, and its methylation levels decreased for exposed but increased for non-exposed. This result was consistent across sensitivity analyses. Enriched Gene Ontology pathways for differentially methylated sites included cardiac function and neurodevelopmental processes. Top CpG sites tended to have overall low levels of DNA methylation, decreasing in exposed, increasing in non-exposed individuals. There were no gene-wide corrected findings for and . This is the first study to identify changes in DNA methylation associated with bullying exposure at the epigenome-wide significance level. Consistent with other population-based studies, we do not find evidence for strong associations between bullying exposure and DNA methylation.

摘要

儿童中的欺凌行为普遍存在,并与广泛的心理健康问题相关。然而,对于接触欺凌后发生变化的生物学途径知之甚少。在基于人群的“R世代研究”和“雅芳亲子纵向研究”(合并样本量 = 1352)的纵向研究中,对欺凌暴露前后外周血中DNA甲基化的全基因组变化进行了研究。对线性混合模型结果进行荟萃分析,以估计DNA甲基化如何随欺凌暴露而变化。进行了敏感性分析,包括同时存在的儿童特征和风险,以及基因本体分析。对注释到[具体基因名称1]和[具体基因名称2]的CpG(胞嘧啶-磷酸-鸟嘌呤)位点进行了候选随访。一个位点cg17312179显示出与欺凌暴露相关的DNA甲基化微小变化(β = -2.67e-03,标准误 = 4.97e-04,P = 7.17e-08)。该位点注释到[具体基因名称1],这是一个与高尔基体功能相关的癌基因,其甲基化水平在暴露组中降低,而在未暴露组中升高。这一结果在敏感性分析中是一致的。差异甲基化位点的富集基因本体途径包括心脏功能和神经发育过程。顶级CpG位点的DNA甲基化总体水平较低,在暴露个体中降低,在未暴露个体中升高。对于[具体基因名称1]和[具体基因名称2]没有全基因组校正的结果。这是第一项在全基因组水平上鉴定出与欺凌暴露相关的DNA甲基化变化的研究。与其他基于人群的研究一致,我们没有发现欺凌暴露与DNA甲基化之间存在强关联的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b6c/7574379/e01150d96f16/KEPI_A_1719303_F0001_OC.jpg

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