Two⁃sample Mendelian randomization analysis of the causal relationship between intestinal flora and rheumatic heart valve disease

PAN Zhihao; LING Yi; WANG Yanggan

doi:10.14188/j.1671-8852.2024.0399

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Two⁃sample Mendelian randomization analysis of the causal relationship between intestinal flora and rheumatic heart valve disease

更新时间：2026-11-05

- Two⁃sample Mendelian randomization analysis of the causal relationship between intestinal flora and rheumatic heart valve disease
- Medical Journal of Wuhan University Vol. 46, Issue 7, Pages: 863-869(2025)
- 作者机构：
  
  1.武汉大学中南医院，心血管内科，湖北武汉 430071
  2.武汉大学中南医院，综合医疗科，湖北武汉 430071
  3.武汉大学医学研究院湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0399
  CLC： R541.2
- Received：22 May 2024，
  
  Published：25 July 2025
- 稿件说明：
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潘治豪,凌懿,王扬淦.两样本孟德尔随机化分析肠道菌群与风湿性心脏瓣膜病的因果关系[J].武汉大学学报（医学版）,2025,46(07):863-869.

PAN Zhihao,LING Yi,WANG Yanggan.Two⁃sample Mendelian randomization analysis of the causal relationship between intestinal flora and rheumatic heart valve disease[J].Medical Journal of Wuhan University,2025,46(07):863-869.
潘治豪,凌懿,王扬淦.两样本孟德尔随机化分析肠道菌群与风湿性心脏瓣膜病的因果关系[J].武汉大学学报（医学版）,2025,46(07):863-869. DOI： 10.14188/j.1671-8852.2024.0399.

PAN Zhihao,LING Yi,WANG Yanggan.Two⁃sample Mendelian randomization analysis of the causal relationship between intestinal flora and rheumatic heart valve disease[J].Medical Journal of Wuhan University,2025,46(07):863-869. DOI： 10.14188/j.1671-8852.2024.0399.

摘要

目的

采用两样本孟德尔随机化的方法评估196种肠道菌群与风湿性心脏瓣膜病（RHVD）之间的潜在因果关系。

方法

数据来源为全基因组关联研究（GWAS）汇总数据，196种肠道菌群包含5 747 754个单核苷酸多样性（SNPs)。风湿性心脏瓣膜病数据包含21 306 347个SNPs。孟德尔随机化分析采用逆方差加权法(IVW)、加权中位数、MR⁃Egger回归三种方法。随后采用异质性检验、水平多效性检验、MR PRESSO法和Leave⁃one⁃out分析检测离群值等进行敏感性分析。

结果

IVW分析结果显示丹毒丝菌纲（

=2.012，95%

: 1.116~3.626，

=0.020）、臭杆菌属（

=2.350，95%

: 1.240~4.456，

=0.009）是RHVD发生的危险因素，而α⁃变形杆菌纲（

=0.610，95%

: 0

.384~0.967，

=0.036）、拟杆菌科S24⁃7（

=0.522，95%

: 0.342~0.798，

=0.003）是RHVD的潜在保护因素。

结论

丹毒丝菌纲、臭杆菌属与风湿性心脏瓣膜病存在正向因果关系，而α⁃变形杆菌纲、拟杆菌科S24⁃7与风湿性心脏瓣膜病存在反向因果关系。

Abstract

Objective

To investigate the potential causal relationship between 196 species of intestinal flora and rheumatic heart valve disease (RHVD) by two⁃sample Mendelian randomization analysis.

Methods

The data source was the Genome⁃Wide Association Study (GWAS) pooled data

and the 196 intestinal flora contained 5 747 754 single nucleotide polymorphisms (SNPs). The rheumatic heart valve disease data contained 21 306 347 SNPs. Mendelian randomization analyses were performed using three methods: inverse variance weighting(IVW)

weighted median

and MR⁃Egger regression. Sensitivity analyses were subsequently performed using the heterogeneity test

horizontal pleiotropy test

MR Presso method

and leave⁃one⁃out analysis to detect outliers.

Results

The results of the IWM analysis showed that

Erysipelotrichia

(

=2.012

95%

:1.116⁃3.626

=0.020) and

Odoribacter

(

=2.350

95%

:1.240⁃4.456

=0.009) were the risk factors for the development of RHVD

whereas

Alphaproteobacteria

(

=0.610

95%

:0.384⁃0.967

=0.036) and

Bacteroidales

S24.7 group (

=0.522

95%

:0.342⁃0.798

=0.003) were potential protective factors for RHVD.

Conclusion

Erysipelotrichia

and

Odoribacter

have a positive causal relationship with RHVD

while

Alphaproteobacteria

and

Bacteroidales

S24.7 group have a negative causal relationship with RHVD

关键词

Keywords

references

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