Associations of the Circulating Levels of Cytokines with Risk of Ankylosing Spondylitis: a Mendelian Randomization Study

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Jan 4

PMID 38173728

Authors

Yang Ye

Chuan-En Wang

Rui Zhong

Xiao-Ming Xiong

Affiliations

Soon will be listed here.

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.

Citing Articles

Causal effects of systemic inflammatory proteins on Guillain-Barre Syndrome: insights from genome-wide Mendelian randomization, single-cell RNA sequencing analysis, and network pharmacology.

Liu J, Pan R Front Immunol. 2024; 15:1456663.

PMID: 39315093 PMC: 11416972. DOI: 10.3389/fimmu.2024.1456663.

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