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

Area of Science:

• Immunology
• Genetics
• Epidemiology

Background:

• The co-occurrence of myasthenia gravis (MG) with other autoimmune conditions is recognized.
• This research investigates potential causal links between MG and five other autoimmune diseases: autoimmune thyroid disease (AITD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1DM).

Purpose of the Study:

• To explore the bidirectional causal relationships between myasthenia gravis and selected autoimmune diseases.
• To determine if MG is a causal factor for other autoimmune conditions, or if they increase the risk of developing MG.

Main Methods:

• A bidirectional Mendelian randomization (MR) study design was employed.
• Utilized seven large-scale genome-wide association studies (GWAS) for MG, AITD (hypothyroidism and hyperthyroidism), MS, RA, SLE, and T1DM.
• Applied multiple statistical methods including inverse-variance-weighted (IVW), weighted-median (WM), MR-Egger regression, and MR-PRESSO for robust analysis and sensitivity testing.

Main Results:

• MG showed a causal association with increased risk for T1DM, SLE, AITD (both subtypes), and MS.
• Conversely, RA, T1DM, and SLE were identified as potential causal factors contributing to the risk of developing MG.
• Bidirectional causal links were specifically supported between MG and SLE/T1DM.

Conclusions:

• This study confirms causal relationships between myasthenia gravis and several other autoimmune diseases.
• Findings highlight a bidirectional causal association between MG and SLE/T1DM.
• Evidence supports MG as a risk factor for AITD and suggests RA as a potential causal driver for MG.