Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian...

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Inflammatory cytokines are associated with inflammatory arthritis like Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA).
• The causal relationship between specific inflammatory cytokines and these conditions requires further elucidation.

Purpose of the Study:

• To investigate the causal relationship between 41 genetic variations of inflammatory cytokines and the risk of developing AS, RA, and PsA using Mendelian randomization (MR).

Main Methods:

• A bidirectional two-sample MR analysis was performed using publicly available genome-wide association study (GWAS) data.
• Genetic summary data for inflammatory cytokines and cases of AS, RA, and PsA from the FinnGen consortium were utilized.
• Inverse variance weighted (IVW) analysis was the primary method, supported by MR Egger, weighted median, and other methods, along with sensitivity analyses.

Main Results:

• Macrophage colony-stimulating factor (MCSF) showed a causal association with increased AS risk.
• TRAIL and beta nerve growth factor (β-NGF) were associated with decreased AS risk.
• Vascular endothelial growth factor (VEGF), IL12p70, IL10, and IL13 were linked to increased PsA risk, while IL-1 receptor antagonist (IL-1rα) was associated with increased seropositive RA risk.

Conclusions:

• This study establishes causal links between specific inflammatory cytokines and inflammatory arthritis.
• Findings offer potential new insights into the etiology, diagnosis, and therapeutic targets for AS, RA, and PsA.