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Published on: December 2, 2022
Causal relationship between chronic inflammatory diseases and uveal melanoma: A bidirectional Mendelian randomization
Yanbing Wang1, Yao Tan2, Zhaochangci Chen2
1Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Purpose:
This study aimed to investigate the causal relationship between chronic inflammatory diseases and uveal melanoma (UVM) and to elucidate the underlying molecular mechanisms and clinical implications.
Methods:
In this bidirectional Mendelian randomization (MR) study, we analyzed the causal relationships between nine common chronic inflammatory diseases and UVM using summary-level genome-wide association study (GWAS) data. The analysis included 342 UVM cases and 378,749 controls from the FinnGen database. For inflammatory diseases, GWAS summary data were obtained from large-scale studies involving up to 484,598 individuals. Functional validation was performed through transcriptomic analysis. Key genes were identified through protein-protein interaction network construction and enrichment analyses, followed by survival analysis to evaluate the association of genes with patient prognosis.
Results:
The forward MR analysis revealed a significant causal relationship between Crohn's disease (CD) and UVM (odds ratio = 1.2, 95% confidence interval: 1.0-1.4, P < 0.05). Sensitivity analysis demonstrated the robustness of the results, with no evidence of heterogeneity or pleiotropy. In reverse MR analysis, UVM showed no significant causal effect on chronic inflammatory diseases. Protein-protein interaction and functional enrichment analyses identified CARD9 and TNFSF15 as potential key genes, and survival analysis revealed that their expression levels were significantly associated with the prognosis of patients with UVM (P < 0.05).
Conclusion:
This study confirmed through MR analysis that CD was a potential risk factor for UVM. Additionally, CARD9 and TNFSF15 were identified as key genes closely associated with patient prognosis, providing new evidence for the pathogenic mechanisms of UVM. These findings were of significant importance for the prevention and control of UVM risk in patients with chronic inflammation, as well as for the development of personalized treatment strategies.
