Myasthenia Gravis and Ischemic Stroke: A Bidirectional Mendelian Randomization Study

Abstract

Background: Autoimmune diseases are associated with cardiovascular and cerebrovascular diseases. However, whether myasthenia gravis (MG) and ischemic stroke (IS) are causally related remains unclear.

Objectives: This study aimed to evaluate potential causal links between MG and IS using bidirectional Mendelian randomization (MR).

Methods: We conducted a two-sample MR analysis to assess the potential associations between MG and IS. Genetic variants associated with MG and IS as well as their subtypes were extracted from genome-wide association studies by meta-analysis. The inverse-variance weighted method was used for the main MR analysis. Sensitivity analyses, including the MREgger, simple mode, simple median, weighted mode, and weighted median approaches were applied to test the robustness of the results.

Results: The MR analyses indicated no causal effects of general MG on IS of all causes (odds ratio [OR] = 0.990, 95% confidence interval [CI]: 0.953-1.029, p = 0.615), large vessel atherosclerosis stroke (OR = 0.943, 95% CI: 0.856-1.039, p = 0.233), cardioembolic stroke (OR = 0.975, 95% CI: 0.867-1.096, p = 0.670), and small vessel occlusion stroke (OR = 1.059, 95% CI 0.974-1.150, p = 0.178). Subgroup analyses indicated no causal effects of early- or late-onset MG on IS and its subtypes (all p > 0.05). The reverse MR analysis showed no significant causal associations of IS on MG (all p > 0.05).

Conclusion: Bidirectional MR analysis did not provide evidence to support a causal relationship between genetically predicted MG and IS, although observational studies have found such a potential link.

Keywords: Myasthenia gravis; causal link; genetics; ischemic stroke; mendelian randomization; single nucleotide polymorphism.