AI Article Synopsis
- - The study investigates the causal relationship between cytokine/growth factor levels and ankylosing spondylitis (AS) using bidirectional Mendelian randomization (MR) with data from large European samples.
- - Key findings revealed that higher levels of specific cytokines (CTACK and MCP-3) are linked to an increased risk of developing AS, while elevated levels of other factors (FGF-basic, G-CSF, and MCP-3) appeared to result from the disease itself.
- - The research supports the idea that targeted treatments for certain cytokines might help prevent or slow down AS, providing genetic evidence for their involvement in the disease process.
Article Abstract
Background: Observational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two.
Methods: Genetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran's Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels.
Results: After Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, = 0.017; β = 0.017, = 0.025; β = 0.053, = 0.025). The results of the sensitivity analysis were generally consistent.
Conclusion: The present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761470 | PMC |
| http://dx.doi.org/10.3389/fimmu.2023.1291206 | DOI Listing |
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