Exploring the Causal Link Between Systemic Lupus Erythematosus and Stroke Risk Through Mendelian Randomization Study

ABSTRACT Introduction Observational studies have indicated an association between systemic lupus erythematosus (SLE) and stroke. However, the genetic causality of this association remains incompletely understood. This study utilizes Mendelian randomization (MR) to investigate the potential causal relationship between SLE and the risk of stroke. Methods We utilized summary‐level statistics data from the largest genome‐wide association studies (GWASs) on SLE and stroke. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with supplementary analyses performed using the MR‐Egger and weighted median (WM) methods. Sensitivity and heterogeneity analyses were additionally performed to ensure the robustness of the results. Results The IVW analysis indicated a potential causal relationship between SLE and an increased risk of any ischemic stroke (odds ratio [OR] = 1.039, 95% confidence interval [CI]: 1.014–1.066, p = 0.002). However, no significant genetic association was observed between SLE and large artery stroke (OR: 1.024, 95% CI: 0.975–1.076, p = 0.326), cardioembolic stroke (OR: 1.014, 95% CI: 0.948–1.085, p = 0.667), small vessel stroke (OR: 0.983, 95% CI: 0.942–1.026, p = 0.458), or intracerebral hemorrhage (OR: 0.992, 95% CI: 0.934–1.054, p = 0.804). Conclusion This MR study provides genetic evidence supporting a causal association between SLE and an increased risk of ischemic stroke. These findings underscore the significance of active monitoring and prevention of ischemic stroke to mitigate cerebrovascular comorbidities in SLE patients. Given the existence of ethnic‐specific genomic heterogeneity, caution is warranted in interpreting these results.