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The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Systemic lupus erythematosus and the risk of cardiovascular diseases: A two-sample Mendelian randomization study
Shuo Huang1, Fugang Huang1, Chunyun Mei1
1The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Insights
This study found no causal link between systemic lupus erythematosus (SLE) and cardiovascular diseases (CVDs). Mendelian randomization analysis confirmed that genetic predisposition to SLE does not increase the risk of developing CVDs.
Area of Science:
- Genetics
- Epidemiology
- Rheumatology
Background:
- Observational studies show inconsistent results regarding the causal role of systemic lupus erythematosus (SLE) in cardiovascular disease (CVD) risk.
- Investigating the causal relationship between SLE and various CVDs is crucial for understanding disease mechanisms and patient outcomes.
Purpose of the Study:
- To investigate the potential causal relationship between systemic lupus erythematosus (SLE) and the risk of cardiovascular diseases (CVDs).
- To utilize a two-sample Mendelian randomization (MR) approach to assess causality, overcoming limitations of previous observational studies.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) analysis using genetic instruments for SLE derived from genome-wide association studies (GWAS).
- Utilized summary statistics for multiple CVDs, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and ischemic stroke (IS) and its subtypes.
- Applied inverse-variance weighted (IVW) as the primary method, supplemented by median, MR-Egger, and MR-PRESSO methods, with comprehensive sensitivity analyses to ensure result robustness.
Main Results:
- Identified 15 single-nucleotide polymorphisms (SNPs) as genetic instruments for SLE after rigorous quality control.
- The primary IVW analysis revealed no statistically significant causal association between genetically predicted SLE and the risk of CAD, MI, AF, IS, cardioembolic stroke, small vessel stroke, or large artery stroke.
- Sensitivity analyses, including MR-Egger intercept and leave-one-out analyses, confirmed the robustness of the findings, indicating no significant pleiotropy or outlier effects.
Conclusions:
- The two-sample Mendelian randomization analysis provides no evidence for a causal association between genetically determined SLE and an increased risk of cardiovascular diseases.
- These findings suggest that SLE may not be a direct causal risk factor for CVDs, challenging previous inconsistent observations.
Background:
Previous observational studies have suggested that the causal role of systemic lupus erythematosus (SLE) in the risk of cardiovascular diseases (CVDs) remained inconsistent. In this study, we aimed to investigate the causal relationship between SLE and CVDs by two-sample Mendelian randomization (MR) analysis.
Methods:
Genetic instruments for SLE were obtained from a public genome-wide association study (GWAS) with 4,036 patients with SLE and 6,959 controls. Summary statistical data for CVDs, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), ischemic stroke (IS), and its subtypes, were identified from other available GWAS meta-analyses. The inverse-variance weighted (IVW) method was used as the primary method to estimate the causal effect. The simple- and weighted-median method, MR-Egger method, and MR pleiotropy residual sum and outlier (MR-PRESSO) were provided as a supplement to the IVW method. Besides, we performed sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis, to evaluate the robustness of the results.
Results:
A total of 15 single-nucleotide polymorphisms (SNPs) were identified after excluding linkage disequilibrium (LD) and potential confounding factors. According to the IVW results, our MR study indicated that genetically predicted SLE was not causally connected with the risk of CVDs [CAD: odds ratio (OR) = 1.005, 95% confidence interval (CI) = 0.986-1.024, p-value = 0.619; MI: OR = 1.002, 95% CI = 0.982-1.023, p-value = 0.854; AF: OR = 0.998, 95% CI = 0.982-1.014, p-value = 0.795; IS: OR = 1.006, 95% CI = 0.984-1.028, p-value = 0.621; cardioembolic stroke (CES): OR = 0.992, 95% CI = 0.949-1.036, p-value = 0.707; small vessel stroke (SVS): OR = 1.014, 95% CI = 0.964-1.067, p-value = 0.589; large artery stroke (LAS): OR = 1.030, 95% CI = 0.968-1.096, p-value = 0.352]. Analogical findings could be observed in supplementary MR methods. Sensitivity analyses suggested that the causal estimates were robust.
Conclusion:
Our two-sample MR analysis provided no evidence that genetically determined SLE was causally associated with the risk of CVDs.
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