Abstract
Abstract
Environmental exposures shape disease risk, but the generalizability of circulating protein-based readouts of exposures across diverse populations remains unknown. Using plasma proteomic profiles of 5,416 proteins in 10,043 participants from the
All of Us
Research Program, we evaluated associations with and composite scores of 100+ exposures, spanning adiposity, air pollution, ambient temperature, and substance use. We find that proteomic exposure signatures are largely consistent across populations and socioeconomic strata, with 2.5
protein scores captured within-region exposure variation and outperformed geographic and socioeconomic correlates, but spatial confounders remain embedded within protein-environment associations. Scores trained in UK Biobank transferred to
All of Us
for biologically proximal exposures, supporting cross-biobank portability. These findings establish plasma proteomics as a scalable framework for exposure measurement across diverse populations, while underscoring that responsible applications require careful consideration of biological context, social patterning, and cohort structure.