Ramírez, Julia;
Van Duijvenboden, Stefan;
Orini, Michele;
Lambiase, Pier D;
Tinker, Andrew;
Young, William J;
Munroe, Patricia B;
(2024)
Prediction of atrial and ventricular arrhythmias using multiple cardiovascular risk-factor polygenic risk scores.
Heart Rhythm
10.1016/j.hrthm.2024.12.017.
(In press).
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Abstract
BACKGROUND: Atrial fibrillation (AF) prediction improves by combining clinical scores with a polygenic risk score (PRS) for AF (AF-PRS), but there are limited studies of PRS for ventricular arrhythmia (VA) prediction. OBJECTIVE: We assessed the value of including multiple PRS for cardiovascular risk factors (CV-PRS) for incident AF and VA prediction. METHODS: We used 158,733 individuals of European ancestry from UK Biobank to build three models for AF: CHARGE-AF (AF1), AF1 + AF-PRS (AF2), AF2 + CV-PRS (AF3). Models for VA included sex and age (VA1), VA1 + coronary artery disease (CAD) PRS (CAD-PRS, VA2), and VA2 + CV-PRS (VA3), conducting separate analyses in subjects with and without ischemic heart disease (IHD). Performance was evaluated in individuals of European (N=158,733), African (N=7,200), South Asian (N=9,241) and East Asian (N=2,076) ancestry from UK Biobank. RESULTS: AF2 had a higher C-index than AF1 (0.762 versus 0.746, P<0.001), marginally improving to 0.765 for AF3 (P<0.001, including PRS for heart failure, electrocardiogram and cardiac magnetic resonance measures). In South Asians, AF2 C-index was higher than AF1 (P<0.001). For VA, the C-index for VA2 was greater than VA1 (0.692 versus 0.681, P<0.001) in Europeans, which was also observed in South Asians (P<0.001). VA3 improved prediction of VA in individuals with IHD. CONCLUSION: CV-PRS improved AF prediction compared to CHARGE-AF and AF-PRS. A CAD-PRS improved VA prediction, while CV-PRS contributed in IHD. AF- and CAD-PRS were transferable to individuals of South Asian ancestry. Our results inform of the use of CV-PRS for personalised screening.
| Type: | Article |
|---|---|
| Title: | Prediction of atrial and ventricular arrhythmias using multiple cardiovascular risk-factor polygenic risk scores |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.hrthm.2024.12.017 |
| Publisher version: | https://doi.org/10.1016/j.hrthm.2024.12.017 |
| Language: | English |
| Additional information: | Copyright © 2024 Heart Rhythm Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | UK Biobank, atrial fibrillation, polygenic risk scores, risk prediction, ventricular arrhythmia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10202770 |
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