Circulating cytokines levels and osteoarthritis: A Mendelian randomization study

Area of Science:

• Genetics and Molecular Biology
• Epidemiology
• Rheumatology

Background:

• Observational studies indicate cytokines and growth factors contribute to osteoarthritis (OA) development.
• This research investigates the causal association between circulating levels of these factors and OA incidence.

Purpose of the Study:

• To determine the causal relationship between circulating cytokine and growth factor levels and osteoarthritis (OA).
• To explore associations with specific OA subtypes: knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA).

Main Methods:

• Two-sample Mendelian randomization (MR) analysis was employed.
• Genome-wide association study (GWAS) data from 8,293 Finnish participants for cytokine/growth factor levels.
• GWAS data for K/HOA, KOA, and HOA from large case-control cohorts were utilized.

Main Results:

• Circulating vascular endothelial growth factor (VEGF) showed a suggestive association with increased risk for K/HOA, KOA, and HOA.
• Interleukin (IL)-12p70 levels were suggestively linked to higher risks of K/HOA, KOA, and HOA.
• IL-18 levels were suggestively associated with an increased risk of HOA.

Conclusions:

• The MR analysis provides suggestive evidence for causal links between specific circulating cytokines/growth factors and OA.
• These findings contribute novel insights into the underlying mechanisms and etiology of osteoarthritis.