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动物模型及精神分裂症人类研究中的全基因组DNA甲基化:一项荟萃分析方案

Genome-wide DNA methylation in an animal model and human studies of schizophrenia: a protocol for a meta-analysis.

作者信息

Magwai Thabo, Oginga Fredrick Otieno, Chiliza Bonginkosi, Mpofana Thabisile, Xulu Khethelo Richman

机构信息

Department of Physiology, University of KwaZulu-Natal College of Health Sciences, Durban, South Africa.

Department of Chemical Pathology, University of KwaZulu-Natal College of Health Sciences, Durban, South Africa.

出版信息

BMJ Open Sci. 2022 Aug 25;6(1):e100264. doi: 10.1136/bmjos-2021-100264. eCollection 2022.

DOI:10.1136/bmjos-2021-100264
PMID:36387953
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9644722/
Abstract

INTRODUCTION AND OBJECTIVE

Neuropsychiatric disorders like schizophrenia are heterogeneous in that they occur because of the interaction of factors. These factors include but are not limited to genetic, epigenetic, neurobiological and environmental factors. Methylation of DNA, like other erpigenetic modifications, is risk factors for neuropsychiatric disorders. Candidate gene approach projects have produced contradictory results to find candidate gene methylation. The current genome-wide studies have limitations.

SEARCH STRATEGY

An exhaustive search strategy was designed to recover studies on genome-wide DNA methylation in schizophrenia patients or schizophrenia rat models. The Medline (PubMed), SCOPUS and Web of Science, databases were searched, giving 4077 references in total.

SCREENING AND ANNOTATION

Studies will undergo two phases of screening, title and abstract screening and article screening, for inclusion by two reviewers. A third reviewer will resolve any disagreements in the article screening phase. Data will be collected using the Systematic Review Facility (http://syrf.org.uk/) tool. All included studies will undergo study quality and risk of bias assessment.

DATA MANAGEMENT AND REPORTING

Data will be extracted and used to calculate effect sizes. For the purpose of this meta-analysis, a random effects model will be used to combine effect sizes. Heterogeneity will be assessed, and the sources identified. A risk-of-bias assessment will be carried out to assess the quality of the studies. An assessment of publication bias will also be carried out.

ETHICS AND DISSEMINATION

No ethical approval is required as there are no participants in the study. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and disseminate the findings through publication and conference presentation.

PROSPERO REGISTRATION NUMBER

CRD42021283159.

摘要

引言与目的

精神分裂症等神经精神疾病具有异质性,其发病是多种因素相互作用的结果。这些因素包括但不限于遗传、表观遗传、神经生物学和环境因素。与其他表观遗传修饰一样,DNA甲基化是神经精神疾病的危险因素。候选基因研究项目在寻找候选基因甲基化方面得出了相互矛盾的结果。目前的全基因组研究存在局限性。

检索策略

设计了详尽的检索策略,以检索有关精神分裂症患者或精神分裂症大鼠模型全基因组DNA甲基化的研究。检索了Medline(PubMed)、SCOPUS和Web of Science数据库,共获得4077条参考文献。

筛选与注释

研究将经过两个筛选阶段,即标题和摘要筛选以及文章筛选,由两名评审员进行纳入评估。第三名评审员将解决文章筛选阶段的任何分歧。将使用系统评价工具(http://syrf.org.uk/)收集数据。所有纳入的研究都将进行研究质量和偏倚风险评估。

数据管理与报告

将提取数据并用于计算效应量。为本荟萃分析的目的,将使用随机效应模型合并效应量。将评估异质性并确定其来源。将进行偏倚风险评估以评估研究质量。还将进行发表偏倚评估。

伦理与传播

由于本研究无参与者,因此无需伦理批准。我们将遵循系统评价和荟萃分析的首选报告项目报告指南,并通过发表和会议报告传播研究结果。

PROSPERO注册号:CRD42021283159。

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本文引用的文献

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DNA Methylation and Schizophrenia: Current Literature and Future Perspective.DNA 甲基化与精神分裂症:当前文献与未来展望。
Cells. 2021 Oct 26;10(11):2890. doi: 10.3390/cells10112890.
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Cell type-specific epigenetic links to schizophrenia risk in the brain.大脑中特定细胞类型的表观遗传与精神分裂症风险的关联。
Genome Biol. 2019 Jul 9;20(1):135. doi: 10.1186/s13059-019-1747-7.
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DNA Methylation Reprogramming during Mammalian Development.哺乳动物发育过程中的 DNA 甲基化重编程。
Genes (Basel). 2019 Mar 29;10(4):257. doi: 10.3390/genes10040257.
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Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis.人类大脑皮层转录组的发育和遗传调控揭示了精神分裂症的发病机制。
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Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights.全转录组关联研究精神分裂症和染色质活性,为疾病机制提供了新见解。
Nat Genet. 2018 Apr;50(4):538-548. doi: 10.1038/s41588-018-0092-1. Epub 2018 Apr 9.
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Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood.年轻人的 DNA 甲基化分析:创伤后应激与血液表观遗传变异之间关联的有限证据。
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