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关节病与产后出血之间的关联:一项双向孟德尔随机化研究。

Association between arthropathies and postpartum hemorrhage: a bidirectional Mendelian randomization study.

作者信息

Wu Zhao, Yuan Chengyu, Peng Xue

机构信息

Department of Obstetrics and Gynecology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

出版信息

Front Genet. 2024 Dec 11;15:1448754. doi: 10.3389/fgene.2024.1448754. eCollection 2024.

Abstract

BACKGROUND

Research links arthropathies with adverse pregnancy outcomes. This study aims to explore its connection to postpartum hemorrhage (PPH) through Mendelian randomization (MR) analysis.

METHODS

The study used GWAS data from the IEU OpenGWAS database for PPH and arthropathies. After selecting instrumental variables, bidirectional MR analysis was conducted using MR-Egger, Weighted median, Simple mode, Weighted mode, and IVW methods. Sensitivity analysis was then performed to assess MR results reliability. Finally, enrichment analysis of genes corresponding to arthropathies SNPs in forward MR was conducted to explore their biological function and signaling pathways.

RESULTS

The forward MR results revealed that arthropathies was causally related to PPH, and arthropathies was a risk factor for PPH. Whereas, there was not a causal relationship between PPH and arthropathies by reverse MR analysis. It illustrated the reliability of the MR analysis results by the sensitivity analysis without heterogeneity, horizontal pleiotropy, and SNPs of severe bias by LOO analysis. Furthermore, a total of 33 genes corresponding to SNPs of arthropathies were obtained, which were mainly enriched in regulation of response to biotic stimulus, spliceosomal snRNP complex and ligase activity in GO terms, and natural killer cell-mediated cytotoxicity in KEGG pathways.

CONCLUSION

This study supported that arthropathies was a risk factor for PPH, and the pathways involved the genes corresponding to SNPs were analyzed, which could provide important reference and evidence for further exploring the molecular mechanism between arthropathies and PPH.

摘要

背景

研究表明关节病与不良妊娠结局有关。本研究旨在通过孟德尔随机化(MR)分析探讨其与产后出血(PPH)的关联。

方法

本研究使用了来自IEU OpenGWAS数据库的PPH和关节病的全基因组关联研究(GWAS)数据。选择工具变量后,采用MR-Egger、加权中位数、简单模式、加权模式和逆方差加权(IVW)方法进行双向MR分析。然后进行敏感性分析以评估MR结果的可靠性。最后,对正向MR中与关节病单核苷酸多态性(SNP)对应的基因进行富集分析,以探索其生物学功能和信号通路。

结果

正向MR结果显示,关节病与PPH存在因果关系,关节病是PPH的危险因素。而反向MR分析显示PPH与关节病之间不存在因果关系。通过敏感性分析(留一法分析无异质性、水平多效性和严重偏差的SNP)说明了MR分析结果的可靠性。此外,共获得33个与关节病SNP对应的基因,在基因本体论(GO)术语中主要富集于对生物刺激的反应调节、剪接体snRNP复合物和连接酶活性,在京都基因与基因组百科全书(KEGG)通路中主要富集于自然杀伤细胞介导的细胞毒性。

结论

本研究支持关节病是PPH的危险因素,并分析了与SNP对应的基因所涉及的通路,可为进一步探索关节病与PPH之间的分子机制提供重要参考和依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/770d/11668810/8cc766d9a0c9/fgene-15-1448754-g001.jpg

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