Wang Rui, Cui Xiao-Wei, Zhang Miao, Xu Jian, Bu Chan-Yuan, Zhao Xiang-Yang
Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, 266035, Shandong, China.
Clin Rheumatol. 2025 Jun;44(6):2277-2285. doi: 10.1007/s10067-025-07396-x. Epub 2025 May 3.
To investigate the genetic causal relationship between systemic lupus erythematosus (SLE) and cardiovascular diseases through Mendelian randomization (MR) analysis.
This study employed a two-sample bidirectional MR design. Data were sourced from publicly available genome-wide association study (GWAS) databases. A total of 482,911 European individuals diagnosed with SLE were selected, covering 24,198,877 single-nucleotide polymorphisms (SNPs), along with relevant GWAS summary data for cardiovascular diseases. Genetic variants were used as instrumental variables. The MR analysis was conducted using the TwoSampleMR R package, employing methods including inverse-variance weighting (IVW), weighted median, and MR-Egger to assess the causal relationships. Sensitivity analyses were also performed to verify result robustness.
MR analysis indicated potential causal risk relationships between genetic predisposition to SLE and increased risk of pericarditis and peripheral artery disease (PAD). Conversely, reverse MR analyses did not demonstrate significant causal associations, with IVW estimates indicating no causal relationships between coronary artery disease (OR = 1.038, 95%CI 0.829-1.3, P = 0.745), dilated cardiomyopathy (OR = 1.044, 95%CI 0.907-1.203, P = 0.548), heart failure (OR = 0.991, 95%CI 0.729-1.348, P = 0.956), hypertrophic cardiomyopathy (OR = 0.958, 95%CI 0.896-1.024, P = 0.207), pericarditis (OR = 0.958, 95%CI 0.821-1.118, P = 0.589), or PAD (OR = 1.157, 95%CI 0.625-2.143, P = 0.642) and the risk of SLE.
This study utilizes MR analysis to reveal genetic causal relationships between SLE and cardiovascular complications, specifically pericarditis and PAD. These findings suggest that inflammation control in SLE patients may help prevent pericarditis while managing dyslipidemia could mitigate PAD risk. Key Points • This study utilizes MR analysis to reveal the causal relationships between SLE and conditions such as pericarditis and PAD from a genetic perspective. • It suggests that controlling inflammation in the treatment of SLE can prevent pericarditis, and managing abnormal lipid levels can reduce the risk of PAD.
通过孟德尔随机化（MR）分析研究系统性红斑狼疮（SLE）与心血管疾病之间的遗传因果关系。
本研究采用两样本双向MR设计。数据来源于公开可用的全基因组关联研究（GWAS）数据库。共选取482911名被诊断为SLE的欧洲个体，涵盖24198877个单核苷酸多态性（SNP），以及心血管疾病的相关GWAS汇总数据。基因变异用作工具变量。使用TwoSampleMR R软件包进行MR分析，采用逆方差加权（IVW）、加权中位数和MR-Egger等方法评估因果关系。还进行了敏感性分析以验证结果的稳健性。
MR分析表明，SLE的遗传易感性与心包炎和外周动脉疾病（PAD）风险增加之间存在潜在的因果风险关系。相反，反向MR分析未显示出显著的因果关联，IVW估计表明冠状动脉疾病（OR = 1.038，95%CI 0.829 - 1.3，P = 0.745）、扩张型心肌病（OR = 1.044，95%CI 0.907 - 1.203，P = 0.548）、心力衰竭（OR = 0.991，95%CI 0.729 - 1.348，P = 0.956）、肥厚型心肌病（OR = 0.958，95%CI 0.896 - 1.024，P = 0.207）、心包炎（OR = 0.958，95%CI 0.821 - 1.118，P = 0.589）或PAD（OR = 1.157，95%CI 0.625 - 2.143，P = 0.642）与SLE风险之间不存在因果关系。
本研究利用MR分析揭示了SLE与心血管并发症（特别是心包炎和PAD）之间的遗传因果关系。这些发现表明，控制SLE患者的炎症可能有助于预防心包炎，而管理血脂异常可降低PAD风险。要点 • 本研究利用MR分析从遗传角度揭示了SLE与心包炎和PAD等疾病之间的因果关系。 • 表明在SLE治疗中控制炎症可预防心包炎，管理异常血脂水平可降低PAD风险。
