Large-scale evaluation of proteomic and polygenic risk scores reveals complementary contributions to incident disease prediction.

ABSTRACT: Plasma proteins capture dynamic physiological processes and may offer more immediate insight into disease risk than static genetic predictors. We evaluated the predictive utility of proteomic risk scores (ProRS) versus polygenic risk scores (PRS) across 301 phenotypes in 39,843 participants from the UK Biobank Pharma Proteomics Project. ProRS, trained on prevalent cases, were tested for incident disease and benchmarked against PRS derived from genome-wide association statistics. Among 268 phenotypes with informative signals, ProRS outperformed PRS in 88% of traits (a median C-index improvement of 9.6%), showing strongest gains for circulatory, metabolic, and immune conditions. Combined models further improved prediction, particularly for traits with higher heritability. Longitudinal analys

SUBMITTER: Woerner J 

PROVIDER: S-EPMC12265734 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature