| Title: | Blood protein assessment of leading incident diseases and mortality in the UK Biobank |
| Journal: | Nature Aging |
| Published: | 10 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38987645/ |
| DOI: | https://doi.org/10.1038/s43587-024-00655-7 |
| Citations: | 3 (3 in last 2 years) as of 8 Aug 2024 |
Publication 11678
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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.</p>
14 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
5 Applications
| Application ID | Title |
|---|---|
| 20361 | Comprehensive Phenotype-wide Association Studies (PheWAS)for Genetic Tool Variants relevant to GSK Drug Targets |
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
| 44257 | Survey of Genetic Factors Affecting Disease Risk and Progression. |
| 53639 | Genetics of the comorbidities of cardiometabolic diseases |
| 69804 | Large-scale whole genome sequencing of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease |
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