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Erik Linnér, MD, PhD student. Photo.

Erik Linnér

Doctoral student

Erik Linnér, MD, PhD student. Photo.

Whole genome sequencing in early onset advanced heart failure

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
Show all

Summary, in English

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.

Department/s

  • Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Molecular Epidemiology and Cardiology
  • Molecular Cardiology
  • Cardiovascular Epigenetics
  • Lund Hemodynamic Lab
  • Division of Hematology and Clinical Immunology
  • Cardiovascular Research - Hypertension
  • EpiHealth: Epidemiology for Health
  • Molecular Vascular Physiology
  • Thoracic Surgery
  • Artificial Intelligence and Bioinformatics in Cardiothoracic Sciences (AIBCTS)
  • Heart and Lung transplantation
  • eSSENCE: The e-Science Collaboration
  • Heparin bindning protein in cardiothoracic surgery
  • Division of Clinical Genetics
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Heart Failure and Mechanical Support

Publishing year

2025

Language

English

Publication/Series

Scientific Reports

Volume

15

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics and Genomics (including Gene Therapy)

Keywords

  • Cardiomyopathies
  • Genetics
  • Genomics
  • Heart failure
  • Heart transplantation

Status

Published

Research group

  • Molecular Epidemiology and Cardiology
  • Molecular Cardiology
  • Cardiovascular Epigenetics
  • Lund Hemodynamic Lab
  • Cardiovascular Research - Hypertension
  • Molecular Vascular Physiology
  • Artificial Intelligence and Bioinformatics in Cardiothoracic Sciences (AIBCTS)
  • Heart and Lung transplantation
  • Heparin bindning protein in cardiothoracic surgery
  • Heart Failure and Mechanical Support

ISBN/ISSN/Other

  • ISSN: 2045-2322