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系统性红斑狼疮与骨髓炎之间的关联:一项针对欧洲人群的两样本孟德尔随机化研究。

Systemic lupus erythematosus Association between Osteomyelitis: A two-sample Mendelian randomization study in European population.

作者信息

Hu Minhua, Sun Zhizhong, Tang Xintao, Zeng Wenxing, Yan Hongsong, Jiang Ziwei, Huang Feng

机构信息

Guangzhou University of Chinese Medicine, Guangzhou, China.

The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Heliyon. 2023 Nov 29;9(12):e22999. doi: 10.1016/j.heliyon.2023.e22999. eCollection 2023 Dec.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) has been correlated with osteomyelitis (OM), yet the underlying causal relationship remains poorly understood. This study aims to investigate the causal association between SLE and OM using Mendelian randomization (MR) analysis.

METHODS

Genetic instrumental variables (IVs) correlated with SLE were extracted from a comprehensive genome-wide association study (GWAS) summary database (5201 cases and 9066 controls). OM was considered a SLE phenotype, and summary data from the fast GWA data portal were utilized for the analysis. Eligible IVs were extracted following rigorous quality control measures ( < 5 × 10-8, LD r2>0.001, distance 1 Mb, and  > 10). MR analysis was conducted using the Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods after excluding potential confounders. Cochran's Q was applied for heterogeneity test. Pleiotropy was evaluated through MR-Egger intercept, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and Leave-one-SNP-out analysis.

RESULT

A total of 40 eligible IVs were included for MR analysis. IVW results demonstrated a positive causal association between SLE and OM ( = 0.049,  = 1.167). Heterogeneity analysis reveal no significant heterogeneity in the IVW analysis ( = 0.5503). Pleiotropy tests, including MR-PRESSO global test and MR-Egger intercept, indicated no evidence of pleiotropy in our findings ( > 0.05). Additionally, the Leave-one-SNP-out analysis showed no substantial deviations when removing individual SNPs, thus supporting the robustness of our results.

CONCLUSION

This study establishes a genetic causal relationship between SLE and OM, indicating an increased risk of developing OM in individuals with SLE. Therefore, proactive management of SLE is advised to mitigate the risk of developing OM.

摘要

背景

系统性红斑狼疮(SLE)与骨髓炎(OM)相关,但潜在的因果关系仍知之甚少。本研究旨在使用孟德尔随机化(MR)分析来研究SLE与OM之间的因果关联。

方法

从一个全面的全基因组关联研究(GWAS)汇总数据库(5201例病例和9066例对照)中提取与SLE相关的遗传工具变量(IVs)。将OM视为SLE的一种表型,并利用快速GWA数据门户的汇总数据进行分析。经过严格的质量控制措施(<5×10-8,连锁不平衡r2>0.001,距离1 Mb,且>10)后提取符合条件的IVs。在排除潜在混杂因素后,使用逆方差加权(IVW)、MR-Egger和加权中位数(WM)方法进行MR分析。应用Cochran's Q进行异质性检验。通过MR-Egger截距、MR-多效性残差和离群值(MR-PRESSO)方法以及逐一排除单核苷酸多态性(SNP)分析来评估多效性。

结果

共有40个符合条件的IVs纳入MR分析。IVW结果表明SLE与OM之间存在正因果关联(=0.049,=1.167)。异质性分析显示IVW分析中无显著异质性(=0.5503)。多效性检验,包括MR-PRESSO全局检验和MR-Egger截距,表明我们的研究结果中无多效性证据(>0.05)。此外,逐一排除SNP分析显示去除单个SNP时无实质性偏差,从而支持了我们结果的稳健性。

结论

本研究确立了SLE与OM之间的遗传因果关系,表明SLE患者发生OM的风险增加。因此,建议对SLE进行积极管理以降低发生OM的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6ab/10731233/54ee207908dc/gr1.jpg

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