The Causal Effects Between Circulating Inflammatory Proteins and Osteoarthritis: A Mendelian Randomization and...

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Rheumatology

Background:

• Observational studies suggest a correlation between inflammatory proteins and osteoarthritis (OA).
• The causal relationship and directionality between inflammatory proteins and OA remain unclear.
• This study investigates potential causal links using Mendelian randomization (MR).

Purpose of the Study:

• To analyze the potential causal relationship between circulating inflammatory proteins and osteoarthritis (OA).
• To identify specific inflammatory proteins influencing OA risk.
• To discover novel inflammatory biomarkers for OA diagnosis.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analysis was employed.
• Genome-wide association study (GWAS) data for OA and 91 circulating inflammatory proteins were utilized.
• Transcriptomic analysis identified differentially expressed inflammation-related genes (IRGs) in OA.

Main Results:

• Forward MR indicated that urokinase-type plasminogen activator, adenosine deaminase, C-C motif chemokine 19, interleukin-10 receptor subunit alpha, and latency-associated peptide transforming growth factor beta 1 may lower OA risk.
• Fractalkine, C-X-C motif chemokine 1, hepatocyte growth factor, and interleukin-8 may increase OA risk.
• Reverse MR revealed bidirectional causal effects between specific OA types (hip, knee) and various inflammatory proteins, alongside the identification of six key OA-related IRGs.

Conclusions:

• This study provides evidence supporting a causal relationship between OA and specific circulating inflammatory proteins.
• Identified inflammatory proteins and genes may serve as potential diagnostic biomarkers for osteoarthritis.
• The findings contribute to understanding the inflammatory mechanisms underlying OA.