Causal association between rheumatoid arthritis and interstitial lung disease: A two-sample bidirectional Mendelian...

Area of Science:

• Genetics and Epidemiology
• Rheumatology
• Pulmonology

Background:

• Epidemiological studies suggest a link between rheumatoid arthritis (RA) and interstitial lung disease (ILD).
• The causal nature of this association remains unclear, with possibilities including shared risk factors or direct causality.
• Investigating genetic causality is crucial for understanding the relationship between RA and ILD.

Purpose of the Study:

• To investigate the genetic causality between rheumatoid arthritis (RA) and interstitial lung disease (ILD) using a bidirectional Mendelian randomization approach.
• To determine if RA causally influences the risk of developing ILD.
• To assess if ILD causally influences the risk of developing RA.

Main Methods:

• Employed a two-sample bidirectional Mendelian randomization (MR) design.
• Utilized genome-wide association study (GWAS) data for RA and ILD in the European population.
• Performed sensitivity analyses including inverse variance weighting, weighted median, MR-Egger regression, heterogeneity, and pleiotropy tests.

Main Results:

• Rheumatoid arthritis (RA) was found to significantly increase the risk of interstitial lung disease (ILD) (OR=1.272, P<0.001).
• Interstitial lung disease (ILD) was also associated with an increased risk of rheumatoid arthritis (RA) (OR=1.111, P=0.033).
• Sensitivity analyses supported the robustness of these findings, indicating potential genetic causality.

Conclusions:

• This study provides evidence for a bidirectional genetic causality between rheumatoid arthritis (RA) and interstitial lung disease (ILD).
• The findings suggest that RA and ILD are not merely associated but may influence each other's development through shared genetic pathways.
• These results may have implications for future screening strategies in genetically susceptible individuals.