Exploring the causal relationship between interleukin levels and osteoarthritis: A two-sample Mendelian randomization...

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Osteoarthritis (OA) is a prevalent degenerative joint disease causing pain and disability, particularly in the elderly.
• Interleukins are implicated in OA pathogenesis, but their causal role remains unclear.
• Establishing a causal link is crucial for developing effective OA prevention and diagnostic strategies.

Purpose of the Study:

• To investigate the potential causal relationship between specific interleukins and the development of osteoarthritis (OA).
• To utilize Mendelian randomization (MR) analysis for robust causal inference in OA etiology.
• To provide clinical guidance for OA prevention and diagnosis based on genetic evidence.

Main Methods:

• Mendelian randomization (MR) analysis was employed using genome-wide association study (GWAS) data.
• OA data comprised 826,690 subjects from 9 populations (177,517 with OA).
• Instrumental variables for 16 interleukins were derived from a GWAS of 8293 Europeans, with inverse variance weighting, MR-Egger, weighted median, and weighted mode methods applied.

Main Results:

• A significant causal relationship was identified between Interleukin-6 (IL-6) and osteoarthritis (OA).
• Interleukin-18 (IL-18) also demonstrated a significant causal effect on osteoarthritis (OA).
• Sensitivity analyses, including MR-Egger, weighted median, weighted mode, and leave-one-out tests, confirmed the robustness of these findings, excluding heterogeneity and pleiotropy.

Conclusions:

• This MR analysis provides strong evidence for a causative link between IL-6 and IL-18 and the pathogenesis of OA.
• The findings highlight IL-6 and IL-18 as potential therapeutic targets for OA.
• Further research into the specific mechanisms of interleukins in OA is warranted to inform clinical practice.