Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Whole genome sequencing in early onset advanced heart failure

Linnér, Erik LU ; Czuba, Tomasz LU ; Gidlöf, Olof LU ; Lundgren, Jakob LU ; Bollano, Entela ; Hellberg, Maria ; Celik, Selvi LU ; Pimpalwar, Neha LU ; Rentzsch, Philipp LU and Martorella, Molly LU , et al. (2025) In Scientific Reports 15(1).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiomyopathies, Genetics, Genomics, Heart failure, Heart transplantation
in
Scientific Reports
volume
15
issue
1
article number
4306
publisher
Nature Publishing Group
external identifiers
  • scopus:85218201028
  • pmid:39910139
ISSN
2045-2322
DOI
10.1038/s41598-025-88465-8
language
English
LU publication?
yes
id
df316b92-710d-41a0-bca5-962bab4d0d79
date added to LUP
2025-06-09 10:24:58
date last changed
2025-06-10 03:00:02
@article{df316b92-710d-41a0-bca5-962bab4d0d79,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Linnér, Erik and Czuba, Tomasz and Gidlöf, Olof and Lundgren, Jakob and Bollano, Entela and Hellberg, Maria and Celik, Selvi and Pimpalwar, Neha and Rentzsch, Philipp and Martorella, Molly and Gummesson, Anders and Melander, Olle and Albinsson, Sebastian and Dellgren, Göran and Borén, Jan and Jeppsson, Anders and Lumbers, R. Thomas and Shah, Sonia and Nilsson, Johan and Natarajan, Pradeep and Lappalainen, Tuuli and Levin, Malin and Ehrencrona, Hans and Smith, J. Gustav}},
  issn         = {{2045-2322}},
  keywords     = {{Cardiomyopathies; Genetics; Genomics; Heart failure; Heart transplantation}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Whole genome sequencing in early onset advanced heart failure}},
  url          = {{http://dx.doi.org/10.1038/s41598-025-88465-8}},
  doi          = {{10.1038/s41598-025-88465-8}},
  volume       = {{15}},
  year         = {{2025}},
}