Objective To investigate the genetic causal relationship between systemic lupus erythematosus (SLE) and cardiovascular diseases through Mendelian randomization (MR) analysis. Methods 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. Results 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. Conclusions 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.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> Key Points </entry> </row> <row> <entry align="left" colname="c1"> • 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. </entry> </row> </tbody> </tgroup> </Table>

Association between systemic lupus erythematosus and cardiovascular health based on genetic data

期刊论文
发表日期：

2025年5月3日

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Rui Wang,
Xiao-Wei Cui,
Miao Zhang,
Jian Xu,
Chan-Yuan Bu,
Xiang-Yang Zhao

摘要

Objective

To investigate the genetic causal relationship between systemic lupus erythematosus (SLE) and cardiovascular diseases through Mendelian randomization (MR) analysis.

Methods

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.

Results

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.

Conclusions

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.