Multi-Ancestry Causal Association between Rheumatoid Arthritis and Interstitial Lung Disease: A Bidirectional...

Area of Science:

• Genetics
• Rheumatology
• Pulmonology

Background:

• Rheumatoid arthritis (RA) frequently presents with extra-articular manifestations, notably interstitial lung disease (ILD).
• The causal relationship between RA and ILD has not been previously explored using bidirectional Mendelian randomization (MR).

Purpose of the Study:

• To investigate the bidirectional causal inference between rheumatoid arthritis and interstitial lung disease.
• To utilize a two-sample Mendelian randomization approach to analyze genetic associations.

Main Methods:

• Employed a two-sample bidirectional Mendelian randomization design.
• Utilized summary statistics from genome-wide association studies (GWAS) across European and East Asian ancestries.
• Included large sample sizes: 474,450 for European and 351,653 for East Asian participants.

Main Results:

• Significant evidence indicated that rheumatoid arthritis increases the risk of interstitial lung disease in European (OR=1.08) and East Asian (OR=1.37) ancestries.
• Reverse Mendelian randomization revealed that interstitial lung disease increases the risk of rheumatoid arthritis in European ancestry (OR=1.12).
• No significant association was found for ILD increasing RA risk in East Asian ancestry (OR=1.02), potentially due to limited instrumental variables.

Conclusions:

• Rheumatoid arthritis and interstitial lung disease exhibit a bidirectional causal relationship based on Mendelian randomization analysis of GWAS data.
• The observed associations are specific to genetic predispositions.
• Further research is warranted to explore non-genetic factors influencing the RA-ILD relationship.