Whole genome sequencing in early onset advanced heart failure

Whole genome sequencing in early onset advanced heart failure

Abstract The genetic contributions to early onset heart failure (HF) are incompletely understood. Genetic testing in advanced HF patients undergoing heart transplantation (HTx) may yield clinical benefits, but data is limited. We performed deep-coverage whole genome sequencing (WGS) in 102 Swedish H...

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Main Authors: Erik Linnér, Tomasz Czuba, Olof Gidlöf, Jakob Lundgren, Entela Bollano, Maria Hellberg, Selvi Celik, Neha Pimpalwar, Philipp Rentzsch, Molly Martorella, Anders Gummesson, Olle Melander, Sebastian Albinsson, Göran Dellgren, Jan Borén, Anders Jeppsson, R. Thomas Lumbers, Sonia Shah, Johan Nilsson, Pradeep Natarajan, Tuuli Lappalainen, Malin Levin, Hans Ehrencrona, J. Gustav Smith
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Subjects:
Heart failure
Cardiomyopathies
Genetics
Genomics
Heart transplantation
Online Access:https://doi.org/10.1038/s41598-025-88465-8
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Summary:Abstract The genetic contributions to early onset heart failure (HF) are incompletely understood. Genetic testing in advanced HF patients undergoing heart transplantation (HTx) may yield clinical benefits, but data is limited. We performed deep-coverage whole genome sequencing (WGS) in 102 Swedish HTx recipients. Gene lists were compiled through a systematic literature review. Variants were prioritized for pathogenicity and classified manually. We also compared polygenic HF risk scores to a population-based cohort. We found a pathogenic (LP/P) variant in 34 individuals (34%). Testing yield was highest in hypertrophic (63% LP/P carriers), dilated (40%) and arrhythmogenic right ventricular (33%) cardiomyopathy and lower in ischemic cardiomyopathy (10%). A family history was more common in LP/P variant carriers than in non-carriers but was present in less than half of carriers (44% vs 13%, P < 0.001), whereas age was similar. Polygenic risk scores were similar in HTx recipients and the population cohort. In conclusion, we observed a high prevalence of pathogenic cardiomyopathy gene variants in individuals with early-onset advanced HF, which could not accurately be ruled out by family history and age. In contrast, we did not observe higher polygenic risk scores in early onset advanced HF cases than in the general population.
ISSN:2045-2322

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