| Title: | Multi-trait polygenic risk scores improve genomic prediction of atrial fibrillation across diverse ancestries |
| Journal: | Nature Communications |
| Published: | 5 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42086565/ |
| DOI: | https://doi.org/10.1038/s41467-026-72708-x |
Publication 20165
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Abstract
Polygenic scores can improve atrial fibrillation risk prediction. However, limited accuracy and cross-ancestry transferability hinder clinical translation. Here, we explore several ensemble approaches to generate ancestry-optimized polygenic scores, with development in diverse participants from the All of Us Research Program, BioBank Japan, and three additional cohorts. Our ancestry-specific multi-trait approach particularly improves prediction in South-Asian (odds-ratio/standard deviation 1.5-1.8; area under curve 0.60-0.64; relative R² +71%), Admixed-American (1.5; 0.60; +34%) and African ancestry groups (1.4; 0.57; +56%). Nevertheless, performance remains highest in European and East-Asian ancestries (1.8-2.2; 0.65-0.68), where >50% of SNP-heritability is explained. Improved risk stratification is also observed at the extremes, identifying European and East-Asian ancestry individuals with risk comparable to rare TTN variants (e.g., 6-11% with >4-fold odds). Finally, our scores improve incident risk prediction alongside clinical models. Together, we show that our ancestry-tailored multi-trait polygenic scores advance atrial fibrillation risk prediction and stratification, providing an equitable foundation for implementation.</p>
15 Authors
- Poeya Haydarlou
- Daria R. Kramarenko
- Nobuyuki Enzan
- Marie Klevjer
- Oliver B. Vad
- Marre E. Corver
- Dominic S. Zimmerman
- Koichi Matsuda
- Søren Z. Diederichsen
- Anja Bye
- Jesper H. Svendsen
- Kaoru Ito
- Patrick T. Ellinor
- Connie R. Bezzina
- Sean J. Jurgens
1 Application
| Application ID | Title |
|---|---|
| 176602 | Understanding the molecular and clinical ethology of cardiac arrhythmia and cardiomyopathy. |
Enabling scientific discoveries that improve human health