Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: A Mendelian...

Area of Science:

• Genetics
• Immunology
• Epidemiology

Background:

• Intervertebral disc degeneration (IVDD) is a condition potentially linked to inflammatory cytokines.
• The precise causal relationship between inflammatory cytokines and IVDD requires further investigation.

Purpose of the Study:

• To employ Mendelian randomization (MR) to establish a causal link between inflammatory cytokines and the risk of developing IVDD.
• To identify specific inflammatory cytokines that may influence IVDD risk.

Main Methods:

• Utilized genetic variants associated with inflammatory cytokines from a large-scale genome-wide association study (GWAS) meta-analysis.
• Sourced IVDD data from the FinnGen consortium.
• Applied Inverse-Variance Weighting (IVW) with random effects, complemented by MR-Egger and weighted median methods for robust causal inference.

Main Results:

• Identified a causal association between interferon-gamma (IFN-γ) and IVDD risk (OR=0.870).
• Found causal links for interleukin-1 beta (IL-1b, OR=0.951), interleukin-4 (IL-4, OR=0.946), and interleukin-18 (IL-18, OR=0.964) with IVDD risk.
• Also observed causal associations for granulocyte colony-stimulating factor (GCSF, OR=0.919) and Stromal cell-derived factor 1a (SDF1a, OR=1.072) with IVDD risk.

Conclusions:

• The study provides evidence for a potential causal relationship between six specific inflammatory cytokines and altered IVDD risk.
• Findings suggest that targeting these cytokines could be a future therapeutic strategy for IVDD.