Causal effects of circulating inflammatory proteins on COPD: A Mendelian randomization study.

Authors

Huanyu Long, Dian Chen, Lanhe Chu, Simin Jiang, Shurun Li, Congxi Zhang, Yahong Chen

Published in

Medicine. Volume 105. Issue 27. Pages e49641. Jul 03, 2026.

Abstract

Chronic obstructive pulmonary disease (COPD) is a major public health concern due to its high prevalence, morbidity, and mortality. Although COPD is recognized as a systemic inflammatory disease, the specific circulating inflammatory proteins associated with its development and progression remain poorly understood. We performed a Mendelian randomization (MR) study to investigate the association between circulating inflammatory proteins and COPD risk. Genetic data were obtained from a genome-wide association study of 20,066 COPD cases and 338,303 controls from the FinnGen consortium and circulating inflammatory protein data were derived from a genome-wide association study of 14,824 participants. The inverse-variance weighted method was used as the primary analysis. Depending on the number of available instrumental variables, complementary methods including the Wald ratio, Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were applied to assess robustness. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy using Cochran's Q test, the MR-Egger intercept, MR-PRESSO, and leave-one-out analysis. In addition, cis-acting protein quantitative trait locus -restricted analyses were performed to further reduce potential pleiotropy. Our findings showed that higher genetically predicted levels of CCL28 (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.69-0.99, P = .0394), CD40 (OR = 0.94, 95% CI: 0.89-0.99, P = .0170), and urokinase-type plasminogen activator (OR = 0.91, 95% CI: 0.85-0.99, P = .0212) were associated with a lower risk of COPD, whereas higher levels of Flt3L (OR = 1.09, 95% CI: 1.01-1.18, P = .0344) and CD6 (OR = 1.06, 95% CI: 1.02-1.12, P = .0099) were associated with a higher risk. Sensitivity analyses showed no evidence of heterogeneity or directional pleiotropy, and leave-one-out analyses indicated that the results were not driven by any single nucleotide polymorphism. These findings suggest that circulating inflammatory proteins, including CCL28, CD40, urokinase-type plasminogen activator, Flt3L, and CD6, may be involved in COPD pathogenesis. Further studies are needed to validate these findings and clarify their potential biological relevance.

PMID:
42410858
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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