Genetically predicted inflammatory cytokines and bone health outcomes: A 2-sample Mendelian randomization study

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Rheumatology

Background:

• Inflammatory factors are linked to bone health, but causal relationships are unclear.
• Investigating these links is crucial for understanding bone diseases.

Purpose of the Study:

• To investigate the causal effects of 41 circulating inflammatory factors on five bone health outcomes using 2-sample Mendelian randomization.
• To identify specific inflammatory cytokines that may influence osteoarthritis, osteoporosis, and rheumatoid arthritis.

Main Methods:

• Utilized publicly available genome-wide association study summary statistics for inflammatory factors and bone health outcomes.
• Employed 2-sample Mendelian randomization with inverse-variance weighted, MR-Egger, and weighted median analyses.
• Conducted sensitivity analyses to assess pleiotropy, heterogeneity, and linkage disequilibrium.

Main Results:

• Genetically predicted IP-10 showed an association with increased odds of osteoarthritis (OA).
• GROA was associated with slightly increased odds of osteoporosis (OP).
• Inverse associations were observed for G-CSF with knee OA, SCF with hip OA, IL-5 with RA, and PDGF-BB with RA.

Conclusions:

• Suggests potential genetically predicted associations between specific inflammatory cytokines and bone health outcomes.
• Highlights the need for larger cytokine genome-wide association studies and independent validation for clinical translation.
• Found no strong evidence of directional pleiotropy in the observed associations.