Causal association between sarcopenia-related traits and osteoarthritis: A bidirectional 2-sample Mendelian...

Area of Science:

• Genetics and Musculoskeletal Health
• Epidemiology and Biostatistics

Background:

• Observational studies suggest a link between sarcopenia and osteoarthritis (OA) pathogenesis.
• Understanding the causal relationship is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the bidirectional causal associations between sarcopenia-related traits and knee and hip OA.
• To utilize Mendelian randomization (MR) to assess genetic links between these conditions.

Main Methods:

• A 2-sample MR study design was employed.
• Instrumental variables for sarcopenia traits (grip strength, lean mass, walking pace) were derived from large genome-wide association studies (GWAS).
• OA data (knee and hip) were obtained from GWAS meta-analyses, with inverse-variance weighted (IVW) as the primary analysis method.

Main Results:

• Genetically predicted faster usual walking pace showed a significant inverse association with both hip OA (OR=0.30) and knee OA (OR=0.20).
• Hip OA demonstrated a significant negative causal effect on usual walking pace (beta=-0.027).
• No significant causal effects were found for grip strength or appendicular lean mass on OA, or vice versa.

Conclusions:

• Usual walking pace, a sarcopenia-related trait, has a protective causal effect against knee and hip OA.
• Hip OA may causally influence slower walking pace.
• Further research is warranted to elucidate the mechanisms and identify potential therapeutic targets for sarcopenia and OA.