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m6A 甲基化与重度抑郁症的关联研究。

An association study of m6A methylation with major depressive disorder.

机构信息

Dalian Seventh People's Hospital, No. 179 Lingshui Road, Ganjingzi District, Dalian City, Liaoning Province, PR China.

Dalian No. 3 People's Hospital, Department of Interventional Radiology, Dalian, PR China.

出版信息

BMC Psychiatry. 2024 May 7;24(1):342. doi: 10.1186/s12888-024-05760-w.

DOI:10.1186/s12888-024-05760-w
PMID:38714976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11075325/
Abstract

OBJECTIVE

To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD).

METHODS

Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated.

RESULTS

Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed.

CONCLUSION

Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

摘要

目的

寻找 N6-甲基腺苷(m6A)基因与重度抑郁症(MDD)之间的关系。

方法

首先鉴定正常和 MDD 样本之间 m6A 相关基因的差异表达。然后对这些基因的功能以及它们可能影响的途径进行分析。使用这些差异基因的表达矩阵构建诊断模型,并使用列线图可视化。同时,使用这些 m6A 相关基因的表达对所有患者进行无监督分类。然后,计算不同簇之间的常见差异基因。通过分析簇间常见差异表达基因的功能,阐明 m6A 相关基因在 MDD 患者发病机制中的作用。

结果

在 MDD 组和对照组之间观察到 ELAVL1 和 YTHDC2 的差异表达。ELAVL1 与 MDD 患者的共病焦虑有关。基于这两个基因的线性回归模型可以准确预测 GSE98793 数据集患者是否患有 MDD,并且可以为临床决策提供净收益。基于 ELAVL1 和 YTHDC2 的表达矩阵,将 MDD 患者分为三个聚类。在这些聚类中,有 937 个常见的差异基因。对这些基因进行了富集分析。应用 ssGSEA 方法预测 GSE98793 数据集样本中 23 种免疫细胞的含量。分析这些免疫细胞与 ELAVL1、YTHDC2 和不同聚类之间的关系。

结论

在所有 m6A 基因中,ELAVL1 和 YTHDC2 与 MDD 密切相关,ELAVL1 与 MDD 共病焦虑有关。ELAVL1 和 YTHDC2 与 MDD 中的免疫细胞呈相反的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56c/11075325/4b17a4e9dc54/12888_2024_5760_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56c/11075325/ac2a37b01f7e/12888_2024_5760_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56c/11075325/4b17a4e9dc54/12888_2024_5760_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56c/11075325/ac2a37b01f7e/12888_2024_5760_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56c/11075325/4b17a4e9dc54/12888_2024_5760_Fig2_HTML.jpg

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