Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis

Area of Science:

• Genetics and Molecular Biology
• Gerontology and Geriatrics
• Immunology

Background:

• Observational studies suggest a link between circulating cytokines and sarcopenia.
• The causal relationship between cytokines and sarcopenia remains unclear.
• Genetic data can elucidate causal links.

Purpose of the Study:

• To investigate the causal relationship between circulating cytokines and sarcopenia-related traits.
• To utilize Mendelian Randomization (MR) for causal inference.
• To analyze genetic associations with appendicular lean mass (ALM) and grip strength.

Main Methods:

• Two-sample bidirectional MR analysis in European ancestry individuals.
• Utilized genome-wide association studies (GWAS) data.
• Employed multiple MR methods (IVW, Weighted Median, MR-Egger, etc.) and sensitivity analyses (Cochran's Q, MR-PRESSO).

Main Results:

• Genetically predicted interleukin-16 levels showed a causal association with both ALM and grip strength.
• Other cytokines (IP-10, IL-1β, HGF, VEGF, IL-12, IL-5) were correlated with sarcopenia traits.
• Sensitivity analyses confirmed robustness and absence of significant pleiotropy.

Conclusions:

• Inflammatory cytokines exert a significant causal effect on sarcopenia.
• Findings suggest potential novel therapeutic targets for sarcopenia.
• Further research in diverse populations is needed to broaden generalizability.