Myasthenia gravis and five autoimmune diseases: a bidirectional Mendelian randomization study.

backgroundThe association between myasthenia gravis (MG) and other autoimmune diseases is well established. In this study, we aimed to investigate the causal effects between MG and five other autoimmune diseases, including autoimmune thyroid disease (AITD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1DM).

methodsWe conducted a bidirectional Mendelian randomization (MR) study by using seven published genome-wide association studies (GWAS), including MG (1873 patients versus 36,370 controls), AITD (autoimmune hypothyroidism) (22,997 patients versus 175,475 controls), AITD (autoimmune hyperthyroidism) (962 patients versus 172,976 controls), MS (47,429 patients versus 68,374 controls), RA (14,361 patients versus 43,923 controls), SLE (4222 patients versus 8431 controls), and T1DM (9266 patients versus 15,574 controls). We used the inverse-variance-weighted (IVW) method, weighted-median (WM) estimator, MR-Egger regression, and MR PRESSO in our analyses. We also carried out detailed sensitivity analyses for each direction using the aforementioned methods.

resultsWhen MG was treated as the exposure, MR evidence suggested a causal relationship between MG and T1DM, SLE, AITD (both hypothyroidism and hyperthyroidism), and MS (excluding RA). Using the IVW method, we found that MG was associated with increased risk of T1DM (OR = 1.94; 95% CI, 1.16-3.26; p = 0.012), SLE (OR = 1.47; 95% CI, 1.02-2.13; p = 0.04), AITD (hypothyroidism) (OR = 1.31; 95% CI, 1.02-1.68; p = 0.039), AITD (hyperthyroidism) (OR = 1.55; 95% CI, 1.15-2.09; p = 0.004), and MS (OR = 1.46; 95% CI, 1.01-2.09; p = 0.041). When MG was treated as the outcome, MR evidence suggested that RA, T1DM, and SLE were causal factors in MG. Using the IVW method, we found that the risk of MG increased with exposure to RA (OR = 1.21; 95% CI, 1.08-1.37; p = 0.002), T1DM (OR = 1.09; 95% CI, 1.02-1.16; p = 0.006), and SLE (OR = 1.12; 95% CI, 1.02-1.23; p = 0.018).

conclusionsThis study demonstrated a causal relationship between MG and several other autoimmune diseases. Our results supported a bidirectional causal association between MG and SLE/T1DM. Our findings also provided reliable evidence that MG is associated with increased risk of AITD. Meanwhile, we also showed that RA is a possible causal driver of MG risk.