Systemic lupus erythematosus and the risk of cardiovascular diseases: A two-sample Mendelian randomization study.

Abstract

BackgroundPrevious 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.MethodsGenetic 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.ResultsA 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.ConclusionOur two-sample MR analysis provided no evidence that genetically determined SLE was causally associated with the risk of CVDs.