Graves' Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Area of Science:

• Genetics
• Immunology
• Epidemiology

Background:

• Graves' disease (GD) and rheumatoid arthritis (RA) frequently co-occur.
• The causal relationship between GD and RA remains unclear.
• Observational studies suggest a link, but evidence for causality is lacking.

Purpose of the Study:

• To investigate the potential bidirectional causal effect between Graves' disease and rheumatoid arthritis.
• To utilize genome-wide association study (GWAS) data for causal inference.
• To provide evidence for clinical screening and management strategies.

Main Methods:

• Genome-wide association study (GWAS) summary data for GD and RA were obtained from the BioBank Japan (BBJ).
• Single nucleotide polymorphisms (SNPs) at genome-wide significance (P < 5.0 × 10^-8) were used as instrumental variables (IVs).
• Mendelian randomization methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, were employed to assess causality and pleiotropy.

Main Results:

• A bidirectional causal effect was identified between Graves' disease and rheumatoid arthritis in an Asian population.
• Rheumatoid arthritis was associated with a 39% increased risk of Graves' disease (OR 1.39, P=0.007).
• Graves' disease showed a 30% increased risk of rheumatoid arthritis (OR 1.30, P=0.112), though not statistically significant.

Conclusions:

• The findings support a bidirectional causal relationship between GD and RA.
• Clinical screening for GD in RA patients, and vice versa, is warranted.
• Effective management of RA in GD patients may offer therapeutic benefits, and RA treatments could potentially be explored for GD.