Blood Protein Assessment of Leading Incident Diseases and Mortality in the UK Biobank

Overview

Journal Nat Aging

Specialty Geriatrics

Date 2024 Jul 10

PMID 38987645

Authors

Danni A Gadd

Robert F Hillary

Zhana Kuncheva

Tasos Mangelis

Yipeng Cheng

Manju Dissanayake

Romi Admanit

Jake Gagnon

Tinchi Lin

Kyle L Ferber

Heiko Runz

Christopher N Foley

Riccardo E Marioni

Benjamin B Sun

Affiliations

Soon will be listed here.

Abstract

The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality in the UK Biobank (n = 47,600). We report 3,209 associations between 963 protein levels and 21 incident outcomes. Next, protein-based scores (ProteinScores) are developed using penalized Cox regression. When applied to test sets, six ProteinScores improve the area under the curve estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperforms a polygenic risk score and HbA1c-a clinical marker used to monitor and diagnose type 2 diabetes. The performance of scores using metabolomic and proteomic features is also compared. These data characterize early proteomic contributions to major age-related diseases, demonstrating the value of the plasma proteome for risk stratification.

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