A polygenic risk score for the QT interval is an independent predictor of drug-induced QT prolongation

Steven T Simon, Meng Lin, Katy E Trinkley, Ryan Aleong, Nicholas Rafaels, Kristy R Crooks, Michael J Reiter, Christopher R Gignoux and Michael A Rosenberg

PLOS ONE, 2024, vol. 19, issue 6, 1-15

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

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0303261

DOI: 10.1371/journal.pone.0303261

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