Combining polygenic and clinical risk scores in atrial fibrillation risk prediction: Implications for population screening

Segan, L; Ho Ho, WW; Crowley, R; William, J; Cho, K; Prabh, S; Chieng, D; Sugumar, H; Voskoboinik, A; Ling, LH; Kalman, JM; Abrams, D; Fatkin, D; Takeuchi, F; Kistler, PM

doi:10.1016/j.hrthm.2025.04.032

Arrhythmias & electrophysiology

Combining polygenic and clinical risk scores in atrial fibrillation risk prediction: Implications for population screening

Heart RhythmPublished 25 Apr 2025Regression analysis

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Authors' conclusion

Combining genetic and clinical risk using the HARMS2-AF and CHARGE-AF risk scores significantly improved AF risk prediction. Incorporating polygenic to clinical-risk scores may enhance population screening and promote targeted interventions to reduce the incidence of AF.

Study context

Population: United Kingdom Biobank participants with available whole genome sequencing dataparticipants with available whole genome sequencing data
Participants: 285,734 participants

Comparison: AF-PRS combined with the HARMS2-AF and Cohorts for Heart and Aging Research in Genetic Epidemiology for AF (CHARGE-AF) risk scores and atrial fibrillation (AF) risk
Outcome: Incident AF
Follow-up: Median 12.9 years

Main finding

As reported in the abstract

AF incidence

6.6%

Median time to AF

8.5

5.0–11.2

Further findings

Incident AF risk, by AF-PRS tertile

	← Lower risk ←→ Higher risk →	HR (95% CI)	P value
High AF-PRS tertile	0.20.5125	2.75 (2.62–2.89)	P < 0.001
	0.20.5125Hazard ratio (log scale)

Outcome	Values
AF risk prediction, HARMS2-AF with AF-PRS	HARMS2-AF AUC 0.828 · HARMS2-AF + AF-PRS AUC 0.839
AF risk prediction, CHARGE-AF with AF-PRS	CHARGE-AF AUC 0.808 · CHARGE-AF + AF-PRS AUC 0.828

AF risk prediction, HARMS2-AF with AF-PRS — Overall net reclassification index: 13.5% (12.8%-14.1%)
AF risk prediction, CHARGE-AF with AF-PRS — Overall net reclassification index: 7.3% (6.7%-7.9%)

Incident AF risk, by AF-PRS tertile: after adjustment for clinical-risk factors; comparator not stated
AF risk prediction, HARMS2-AF with AF-PRS: DeLong P<.001
AF risk prediction, CHARGE-AF with AF-PRS: DeLong P<.001

Original publication

Combining polygenic and clinical risk scores in atrial fibrillation risk prediction: Implications for population screening. Heart Rhythm. Published 25 April 2025. doi:10.1016/j.hrthm.2025.04.032

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