Heart & lung : the journal of critical care · 2025
The genetic support for the causal relationship between 91 circulating inflammatory proteins and pneumothorax: A two-sample mendelian randomization study.
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Zhou Changshuai, Zhang Ran
Аннотация
BACKGROUND: Pneumothorax, a common pleural disease, has an unclear pathogenesis. Observational studies suggest that inflammation may directly or indirectly contribute to the development of pneumothorax.
OBJECTIVES: To investigate the causal relationship between circulating inflammatory proteins and pneumothorax using Mendelian randomization (MR) analysis.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis by combining genome-wide association study (GWAS) data on 91 circulating inflammatory proteins with pneumothorax GWAS data. Five MR methods were applied: Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Directionality was assessed using the MR Steiger test. Sensitivity analyses included Cochran' s Q test, the MR-PRESSO global test, the MR-Egger regression intercept test, and a leave-one-out analysis. To further mitigate confounding, multivariable MR analyses were conducted using GWAS data on biological and phenotypic age as covariates.
RESULTS: Four inflammatory proteins were causally associated with pneumothorax. Protective proteins included Interleukin-17A (IL-17A) [OR = 0.83, 95 % CI (0.69, 0.99), p = 0.04] and SIR2-like protein 2 (SIRT2) [OR = 0.72, 95 % CI (0.57, 0.93), p = 0.01]. Risk-associated proteins included Interleukin-13 (IL-13) [OR = 1.23, 95 % CI (1.03, 1.47), p = 0.02] and TNF-related apoptosis-inducing ligand (TRAIL) [OR = 1.22, 95 % CI (1.02, 1.44), p = 0.02]. Multivariable MR confirmed the robustness of the associations, particularly for IL-13. Sensitivity analyses revealed no substantial pleiotropy or heterogeneity.
CONCLUSIONS: The results yield novel perspectives on the etiological association between systemic inflammatory mediators and pneumothorax pathogenesis, potentially identifying candidate biomarkers for risk stratification and therapeutic targeting in pneumothorax management.
OBJECTIVES: To investigate the causal relationship between circulating inflammatory proteins and pneumothorax using Mendelian randomization (MR) analysis.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis by combining genome-wide association study (GWAS) data on 91 circulating inflammatory proteins with pneumothorax GWAS data. Five MR methods were applied: Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. Directionality was assessed using the MR Steiger test. Sensitivity analyses included Cochran' s Q test, the MR-PRESSO global test, the MR-Egger regression intercept test, and a leave-one-out analysis. To further mitigate confounding, multivariable MR analyses were conducted using GWAS data on biological and phenotypic age as covariates.
RESULTS: Four inflammatory proteins were causally associated with pneumothorax. Protective proteins included Interleukin-17A (IL-17A) [OR = 0.83, 95 % CI (0.69, 0.99), p = 0.04] and SIR2-like protein 2 (SIRT2) [OR = 0.72, 95 % CI (0.57, 0.93), p = 0.01]. Risk-associated proteins included Interleukin-13 (IL-13) [OR = 1.23, 95 % CI (1.03, 1.47), p = 0.02] and TNF-related apoptosis-inducing ligand (TRAIL) [OR = 1.22, 95 % CI (1.02, 1.44), p = 0.02]. Multivariable MR confirmed the robustness of the associations, particularly for IL-13. Sensitivity analyses revealed no substantial pleiotropy or heterogeneity.
CONCLUSIONS: The results yield novel perspectives on the etiological association between systemic inflammatory mediators and pneumothorax pathogenesis, potentially identifying candidate biomarkers for risk stratification and therapeutic targeting in pneumothorax management.