| Title: | Cross-biobank generalizability and accuracy of electronic health record-based predictors compared to polygenic scores |
| Journal: | Nature Genetics |
| Published: | 27 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40866628/ |
| DOI: | https://doi.org/10.1038/s41588-025-02298-9 |
| URL: | https://www.nature.com/articles/s41588-025-02298-9.pdf |
Publication 19650
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Abstract
Electronic health record (EHR)-based phenotype risk scores (PheRS) leverage individuals' health trajectories to estimate disease risk, similar to how polygenic scores (PGS) use genetic information. While PGS generalizability has been studied, less is known about PheRS generalizability across healthcare systems and whether PheRS are complementary to PGS. We trained elastic-net-based PheRS to predict the onset of 13 common diseases for 845,929 individuals (age = 32-70 years) from three biobank-based studies in Finland (FinnGen), the UK (UKB) and Estonia (EstB). All PheRS were statistically significantly associated with the diseases of interest and most generalized well without retraining when applied to other studies. PheRS and PGS were only moderately correlated and models including both predictors improved onset prediction compared to PGS alone for 8 of 13 diseases. Our results indicate that EHR-based risk scores can transfer well between EHRs, capture largely independent information from PGS, and provide additive benefits for disease risk prediction.</p>
14 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Electronic Health Records
- Estonia
- Female
- Finland
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Multifactorial Inheritance
- Phenotype
- United Kingdom
9 Authors
- Kira E. Detrois
- Tuomo Hartonen
- Maris Teder-Laving
- Bradley Jermy
- Kristi Läll
- Zhiyu Yang
- Reedik Mägi
- Samuli Ripatti
- Andrea Ganna
1 Application
| Application ID | Title |
|---|---|
| 78537 | International consortium for integrative genomics prediction (INTERVENE) |
Enabling scientific discoveries that improve human health