Proteome-wide association study of air pollution exposures in a high-risk cardiac catheterization cohort
American Journal of Preventive Cardiology, 2026
Liu C., Roberts B., Patel M., Roberts A., Alkhoder A., Ko Y., Jin Z., Yadalam A., Alonso A., Huang J., Schildkraut J., Huels A., Chang H., Marsit C., Liang D., Quyyumi A., Sun Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD Environmental Health & Toxicology | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Background
Ambient air pollution is a modifiable cardiovascular risk factor, but the circulating protein pathways linking pollution exposure to risk among patients with coronary artery disease (CAD) remain unclear.
Methods
We conducted an observational proteome-wide association study with external replication. Discovery analyses included 198 Emory Cardiovascular Biobank (EmCAB) participants undergoing cardiac catheterization. Replication analyses included 2,522 UK Biobank participants with prevalent CAD. Residential PM2.5, nitrogen oxides (NOx), and carbon monoxide (CO) were estimated at participants’ home addresses over 1-year, 1-month, 1-week, and 1-day windows before biospecimen collection in Emory. Annual PM2.5 and NOx were examined in UK Biobank. Multivariable linear regression tested associations between pollutant exposures and plasma proteins, adjusting for demographic and cardiovascular risk factors. Gene Ontology enrichment analyses were performed using selected proteins.
Results
In EmCAB, statistically significant proteomic associations were observed exclusively for the 1-month exposure window: 115 proteins were associated with PM2.5 and 67 with CO at FDR <0.05, whereas none were associated with NOx, and no proteins met FDR <0.05 for the 1-year, 1-week, or 1-day windows. Pathway enrichment implicated mitotic cell cycle for PM2.5 and platelet aggregation, actin filament organization, and mitotic cell cycle for CO. In UK Biobank, seven PM2.5-associated proteins were replicated, including GP5, GLOD4, GP6, PARK7, STIP1, SERPINB1, and SERPINB9.ConclusionsAmong individuals undergoing cardiac catheterization, 1-month PM2.5 and CO exposures were associated with plasma proteomic signatures involving platelet, cytoskeletal, and cell-cycle pathways. Exploratory cross-platform replication provided additional support for several PM2.5-associated proteins in an independent CAD cohort. These findings identify candidate molecular responses to air pollution in a population at high cardiovascular risk.