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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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-88465-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Erik Linnér |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4b1d4a676c1c46158b3926449f87e256 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4b1d4a676c1c46158b3926449f87e2562025-02-09T12:36:29ZengNature PortfolioScientific Reports2045-23222025-02-011511910.1038/s41598-025-88465-8Whole genome sequencing in early onset advanced heart failureErik Linnér0Tomasz Czuba1Olof Gidlöf2Jakob Lundgren3Entela Bollano4Maria Hellberg5Selvi Celik6Neha Pimpalwar7Philipp Rentzsch8Molly Martorella9Anders Gummesson10Olle Melander11Sebastian Albinsson12Göran Dellgren13Jan Borén14Anders Jeppsson15R. Thomas Lumbers16Sonia Shah17Johan Nilsson18Pradeep Natarajan19Tuuli Lappalainen20Malin Levin21Hans Ehrencrona22J. Gustav Smith23Department of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg UniversitySection of Clinical Genetics, Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical ServicesDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Systems Biology, Columbia UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg UniversityDepartment of Internal Medicine, Skåne University HospitalSection of Vascular Physiology, Department of Experimental Medical Science, Lund UniversityDepartment of Thoracic Surgery, Sahlgrenska University HospitalDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg UniversityDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg UniversityInstitute of Health Informatics, University College LondonInstitute for Molecular Bioscience, University of QueenslandDepartment of Thoracic and Vascular Surgery, Skåne University HospitalCardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical SchoolDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg UniversitySection of Clinical Genetics, Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical ServicesDepartment of Cardiology, Clinical Sciences Lund, Lund UniversityAbstract 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.https://doi.org/10.1038/s41598-025-88465-8Heart failureCardiomyopathiesGeneticsGenomicsHeart transplantation |
| spellingShingle | 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 Whole genome sequencing in early onset advanced heart failure Scientific Reports Heart failure Cardiomyopathies Genetics Genomics Heart transplantation |
| title | Whole genome sequencing in early onset advanced heart failure |
| title_full | Whole genome sequencing in early onset advanced heart failure |
| title_fullStr | Whole genome sequencing in early onset advanced heart failure |
| title_full_unstemmed | Whole genome sequencing in early onset advanced heart failure |
| title_short | Whole genome sequencing in early onset advanced heart failure |
| title_sort | whole genome sequencing in early onset advanced heart failure |
| topic | Heart failure Cardiomyopathies Genetics Genomics Heart transplantation |
| url | https://doi.org/10.1038/s41598-025-88465-8 |
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