Whole genome sequencing in early onset advanced heart failure

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.

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Publication Details

Journal
Scientific Reports
Published
2025-02-05
DOI
https://doi.org/10.1038/s41598-025-88465-8
Citations
1
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
Field-Weighted Citation Impact
1.39

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Whole genome sequencing in early onset advanced heart failure

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Scientific Reports
Cardiomyopathy and Myosin Studies
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article

Whole genome sequencing in early onset advanced heart failure

Göran Dellgren, Sebastian Albinsson, Olof Gidlöf, J. G. Smith, Anders Gummesson, Johan Nilsson, Hans Ehrencrona, Sonia Shah, Molly Martorella, Jan Borén, Pradeep Natarajan, Malin Levin, Entela Bollano, Erik Linnér, Tuuli Lappalainen, Anders Jeppsson, Maria Hellberg, Neha Pimpalwar, Jakob Lundgren, Philipp Rentzsch, R Thomas Lumbers, Olle Melander, Selvi Celik, Tomasz Czuba
article en
1 citations

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.

Scientific ReportsVol. 15(1)
Broad Institute (US), Harvard University (US), The University of Queensland (AU), Malmö University (SE), Lund University (SE), Sahlgrenska University Hospital (SE), Massachusetts General Hospital (US), Skåne University Hospital (SE), University College London (GB), Columbia University (US), KTH Royal Institute of Technology (SE), University of Gothenburg (SE)
Regeneron Pharmaceuticals, Stiftelsen för Strategisk Forskning, Fondation pour la Recherche Médicale, Lunds Universitet, Hjärt-Lungfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Science for Life Laboratory, Skånes universitetssjukhus
Good health and well-being
Openalex Percentile: Top 23%
Cardiomyopathy and Myosin Studies
1.39
DOIOpen Access PDFOpenAlex
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