Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization

Area of Science:

• Endocrinology and Immunology
• Genetic Epidemiology

Background:

• Previous studies suggest a link between autoimmune thyroid disease (AITD) and myasthenia gravis (MG), but evidence is limited and controversial.
• The precise causal relationship between AITD and MG remains uncertain, necessitating further investigation.

Purpose of the Study:

• To investigate the potential causal relationship between AITD and MG using a Mendelian randomization (MR) approach.
• To clarify the directionality of the association between AITD and MG.

Main Methods:

• Utilized genome-wide association study (GWAS) summary statistics in European ancestry for MR analysis.
• Employed multiple MR techniques including inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR-PRESSO to ensure result stability.
• Assessed heterogeneity using Cochran's Q value and investigated horizontal pleiotropy via MR-Egger regression and MR-PRESSO.

Main Results:

• The IVW method indicated a causal link between Graves' disease (GD) and MG (OR 1.31) and autoimmune hypothyroidism and MG (OR 1.26).
• Reverse MR analysis confirmed a causal relationship between MG and GD (OR 1.50) but revealed an unstable association between MG and autoimmune hypothyroidism due to horizontal pleiotropy.
• MG showed a higher prevalence of thyroid peroxidase antibody (TPOAb) positivity (OR 1.84) and a potential link to elevated TSH levels (Beta:0.08).

Conclusions:

• Autoimmune thyroid disease patients exhibit increased susceptibility to developing myasthenia gravis.
• Myasthenia gravis patients demonstrate a higher incidence of Graves' disease, suggesting a bidirectional relationship.