Proteomic Signatures of Multiple Environmental Exposures and the Risk of COPD
TL;DR
Both protein scores and specific proteins may partly characterize the proteomic component of the observed associations between exposure and COPD, providing population-based evidence for an environment–proteome–COPD framework.
Abstract
Environmental factors such as air pollution, ambient temperature, and socioeconomic status are associated with chronic obstructive pulmonary disease (COPD), yet the potential role of proteomic alterations remains unclear. We aim to identify circulating proteomic signatures related to distinct environmental exposures and evaluate their associations with incident COPD. We analyzed 42,445 participants from the UK Biobank with baseline plasma proteomic profiling and 21 environmental exposure assessments. Exposure-associated proteins were identified using multivariable linear regression and further selected using repeated LASSO-based stability selection. Exposure-specific proteomic scores were constructed and evaluated for associations with incident COPD using Cox models. Exploratory mediation analyses under a counterfactual framework assessed the potential mediating role of proteomic scores and individual proteins. Multiple environmental exposures were associated with specific proteomic variation, which were subsequently used to construct exposure-specific scores. Both environmental exposures and their protein scores were related to systemic inflammation, lung function, and the subsequent risk of COPD, with the strongest positive association observed for the Townsend deprivation index-related score (HR = 1.80, 95% CI: 1.71–1.90) and an inverse association observed for the NDVI-related score (HR = 0.72, 95% CI: 0.69–0.76). Protein scores explained 41.1% (95% CI: 25.0–57.2), 33.0% (95% CI: 18.8–47.1), and 50.5% (95% CI: 42.1–58.8) of the SO2–COPD, NO2–COPD, and Townsend deprivation index–COPD associations, respectively. At the separate protein level, CDCP1, REG3A, IL15, TNFSF13B, and IL6 repeatedly ranked among the top estimated contributors across multiple exposures. Circulating proteomic profiles capture the biological imprint of environmental factors and are significantly associated with incident COPD. Both protein scores and specific proteins may partly characterize the proteomic component of the observed associations between exposure and COPD, providing population-based evidence for an environment–proteome–COPD framework.