Summary
Objective
The causal relationship between inflammatory cytokines and Osteoarthritis (OA) has
not been well investigated. This study investigated the causal role of inflammatory
cytokines in the risk of OA and total joint arthroplasty using the Mendelian randomization
(MR) method.
Method
Single nucleotide polymorphisms (SNPs) robustly associated with inflammatory cytokines
were used as instrumental variables. The inverse-variance weighted (IVW) method with
false discovery rate (FDR) adjusted P-value (q-value) for multiple comparisons were used as the main MR method to estimate
causal effects based on the summary-level data for OA (knee and hip OA, respectively)
and total joint arthroplasty (TJA). Sensitivity analyses validated the robustness
of the results and ensured the absence of heterogeneity and horizontal pleiotropy.
Results
After FDR adjustment, macrophage colony-stimulating factor (MCSF) and vascular endothelial
growth factor (VEGF) were identified as causally associated with knee OA (MCSF, odds
ratio [OR]: 1.16, 95% confidence interval [CI]: 1.09–1.23, q = 5.05 × 10−5; VEGF, OR: 1.09, 95% CI: 1.04–1.15, q = 0.011). We also observed that genetically predicted MCSF and VEGF were positively
associated with the risk of TJA, and MCP3 was negatively associated with for the risk
of TJA, although the effects seem fairly modest. Sensitivity analysis further excluded
the influence of heterogeneity and horizontal pleiotropy.
Conclusions
Inflammatory cytokines, namely MCSF and VEGF, were causally associated with knee OA,
which could enhance our understanding of inflammation in OA pathology.
Keywords
Abbreviations:
MR (Mendelian randomization), GWAS (Genome-wide association studies), IVW (Inverse-variance weighted), MR-PRESSO (MR pleiotropy residual sum and outlier), SNP (Nucleotide polymorphism), OA (Osteoarthritis), TJA (Total joint arthroplasty), TKA (Total knee arthroplasty), THA (Total hip arthroplasty), MMP3 (Monocyte chemotactic protein-3), MCSF (Macrophage colony-stimulating factor), VEGF (Vascular endothelial growth factor), activePAI (Active plasminogen activator inhibitor), CTACK (Cutaneous T-cell attracting chemokine), GROa (Growth-regulated oncogene-alpha), HGF (Hepatocyte growth factor), MIG (Monokine induced by interferon-gamma), MIP (Macrophage inflammatory protein), PDGFbb (Platelet-derived growth factor BB), RANTES (Regulated upon activation, normal T cell expressed and secreted), SCF (Stem cell factor), SCGFb (Stem cell growth factor beta), SeSelectin (Soluble E-selectin), sICAM (Soluble intercellular adhesion molecule), TRAIL (TNF-related apoptosis inducing ligand)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 16, 2022
Accepted:
December 11,
2022
Received:
May 4,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
