Plasma Proteomic Associations with Short‑, Intermediate‑, and Long-Term Ozone Exposure in a Han Chinese population

While epidemiological evidence consistently links ambient ozone to higher rates of disease and death, the biological mechanism and processes driving this association remain unclear. In this study, we recruited 2623 Han Chinese participants and measured the expression of 6528 plasma proteins using untargeted high-resolution mass-spectrometry-based proteomics. Individual-level ozone exposure was assessed at short-term, intermediate-term, and long-term durations. Proteome-wide association analysis identified 209 proteins significantly associated with ozone exposure across three exposure windows, including 74 proteins for short-term, 52 for intermediate-term, and 125 for long-term. Moreover, comparative analyses of proteins associated with three exposures revealed that longer ozone exposure magnifies proteomic effects. The ozone-related proteins were significantly enriched in biological pathways related to coagulation, vesicle trafficking, and nucleotide metabolism and have previously been linked to a variety of diseases, such as cardiovascular, respiratory, immune, and metabolic diseases. Collectively, our findings offer a proteome-wide perspective on the biological mechanisms underlying ozone toxicity, supported by evidence from a Chinese cohort.