Causal relationship analysis between thoracic lumbosacral disc disease and osteoarthritis based on two⁃sample Mendelian randomization

XING Junwei; LIU Siyi; CHEN Haitao; WEN Yinxian; CHEN Liaobin

doi:10.14188/j.1671-8852.2024.0203

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Causal relationship analysis between thoracic lumbosacral disc disease and osteoarthritis based on two⁃sample Mendelian randomization

更新时间：2026-11-05

- Causal relationship analysis between thoracic lumbosacral disc disease and osteoarthritis based on two⁃sample Mendelian randomization
- Medical Journal of Wuhan University Vol. 46, Issue 6, Pages: 759-765(2025)
- 作者机构：
  
  武汉大学中南医院关节与运动医学科湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0203
  CLC： R684.3
- Received：25 March 2024，
  
  Published：25 June 2025
- 稿件说明：
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邢俊炜,刘思怡,陈海涛等.胸腰骶椎椎间盘病变和骨关节炎的因果关系的双样本孟德尔随机化分析[J].武汉大学学报（医学版）,2025,46(06):759-765.

XING Junwei,LIU Siyi,CHEN Haitao,et al.Causal relationship analysis between thoracic lumbosacral disc disease and osteoarthritis based on two⁃sample Mendelian randomization[J].Medical Journal of Wuhan University,2025,46(06):759-765.
邢俊炜,刘思怡,陈海涛等.胸腰骶椎椎间盘病变和骨关节炎的因果关系的双样本孟德尔随机化分析[J].武汉大学学报（医学版）,2025,46(06):759-765. DOI： 10.14188/j.1671-8852.2024.0203.

XING Junwei,LIU Siyi,CHEN Haitao,et al.Causal relationship analysis between thoracic lumbosacral disc disease and osteoarthritis based on two⁃sample Mendelian randomization[J].Medical Journal of Wuhan University,2025,46(06):759-765. DOI： 10.14188/j.1671-8852.2024.0203.

摘要

目的

通过双向孟德尔随机化分析探究胸腰骶椎椎间盘病变与骨关节炎（OA）的因果关系。

方法

从已发表的全基因组关联研究（GWAS）中选择了椎间盘病变（IDD）、OA相关特征的工具变量。椎间盘病变、手骨关节炎、膝骨关节炎、髋骨关节炎及膝和/或髋骨关节炎的工具变量来自公开全基因组关联研究。通过双样本和多变量孟德尔随机化分析，来探究椎间盘病变与骨关节炎发病风险的因果关联。采用逆方差加权法(IVW)作为主要孟德尔随机化分析方法，采用孟德尔随机化⁃Egger回归、加权中位数法、MR⁃PRESSO等方法检测和校正结果。采用Cochran's

检验来评估异质性，采用MR⁃Egger⁃intercept分析来确定潜在的多效性。

结果

双样本孟德尔随机化的IVW结果显示，以IDD为暴露因素，IDD与膝骨关节炎（

=1.19，95%

：1.08~1.32，

0.05）、膝和/或髋骨关节炎（

=1.12，95%

：1.02~1.22，

0.05）、髋骨关节炎（

=1.15，95%

：1.00~1.31，

0.05）之间呈正向因果效应且具有统计学意义。IDD与手骨关节炎（

=0.59，95%

：0.18~1.99，

0.05）之间没有因果效应。结果表明IDD可能是膝骨关节炎和髋骨关节炎发病及膝和/或髋关节炎的风险因素。以OA为暴露因素，IVW分析结果显示，IDD与膝骨关节炎（

=0.82，95%

：0.63~1.09，

0.05）、膝和/或髋骨关节炎（

=1.15，95%

：1.00~1.33，

0.05）、髋骨关节炎（

=1.07，95%

：1.00~1.14，

0.05）、手骨关节炎（

=0.98，95%

：0.96~1.00，

0.05）之间没有因果效应。结果表明OA不是椎间盘病变发病的风险因素。敏感性分析结果表明因果关系稳健，没有观察到显著的异质性，孟德尔随机化⁃Egger截距分析未检测到潜在的水平多效性。

结论

胸腰骶椎椎间盘病变是膝骨关节炎和髋骨关节炎发病及膝和/或髋关节炎的危险因素，而没有足够的证据表明骨关节炎是椎间盘病变的危险因素。

Abstract

Objective

To investigate the causal relationship between thoracic lumbosacral disc disease and osteoarthritis (OA) by bidirectional Mendelian randomization analysis.

Methods

Instrumental variables related to intervertebral disc disease (IDD) and OA were selected from published genome⁃wide association studies (GWAS). Instrumental variables for disc disease

hand osteoarthritis

knee osteoarthritis

hip osteoarthritis

and knee and/or hip osteoarthritis were derived from publicly available GWAS. Through two⁃sample and multivariate Mendelian randomized analysis

the causal relationship between IDD and the risk of OA was analyzed. The inverse variance weighting(IVW) method was used as the main Mendelian randomization analysis method

and the results are detected and corrected by Mendelian randomization⁃Egger regression

weighted median method

MR⁃PRESSO

etc. Cochran's

test was used to evaluate heterogeneity

and MR⁃Egger⁃intercept analysis was used to determine potential pleiotropy.

Results

The IVW method of two⁃sample Mendelian randomization showed that taking IDD as the exposure factor

IDD was associated with knee osteoarthritis (

=1.19

95%

: 1.08⁃1.32

0.05)

knee and/or hip osteoarthritis (

=1.12

95%

: 1.02⁃1.22

0.0

and hip osteoarthritis (

=1.15

95%

: 1.00⁃1.25

0.05)

with statistical significance. There was no causal effect between IDD and hand osteoarthritis (

=0.59

95%

: 0.18⁃1.99

0.05). The results suggest that IDD may be a risk factor for the onset of knee osteoarthritis

hip osteoarthritis

and knee and/or hip arthritis. Taking OA as the exposure factor

the results of IVW analysis showed that IDD was not associated with knee osteoarthritis (

=0.82

95%

: 0.63⁃1.09

0.05)

knee and/or hip osteoarthritis (

=1.15

95%

: 1.00⁃1.33

0.05) and hand osteoarthritis (

=0.98

95%

: 0.96⁃1.00

0.05). The results showed that OA was not a risk factor for IDD.The sensitivity analysis results showed that the causal relationship was stable

no significant heterogeneity was observed

and no potential horizontal pleiotropy was detected by Mendel randomization ⁃Egger intercept analysis.

Conclusion

IDD is a risk factor for knee osteoarthritis

hip osteoarthritis

knee and/or hip arthritis

but there is insufficient evidence to show that OA is a risk factor for IDD.

关键词

Keywords

references

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