ArticlePloS one2024
A polygenic risk score for the QT interval is an independent predictor of drug-induced QT prolongation.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pharmacogenomic markers associated with drug-induced QT prolongation: a systematic review.PharmacogenomicsPooled it
- Clinical impact of a multidisciplinary remote-based hybrid antibiotic stewardship program in critically ill patients during COVID-19 pandemic in Korea: a prospective pilot implementation study.Antimicrobial resistance and infection control · 2026Article
- Polygenic risk modulates myocardial repolarization and T-wave geometry in congenital long-QT syndrome type 1: evidence from digital ECG phenotyping.Frontiers in cardiovascular medicine · 2026Article
- The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies.Genes · 2025Review
- Impact of an Alert-Based Inpatient Clinical Decision Support Tool to Prevent Drug-Induced Long QT Syndrome: Large-Scale, System-Wide Observational Study.Journal of medical Internet research · 2025Observational
- Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort.Pharmacogenetics and genomics · 2025Article
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9 authors.
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Abstract
Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17-1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS.
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