Year: 2025
Type: article
Study design: Observational Study
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.
Source: Scientific Reports
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
Institutions: Lund University, Skåne University Hospital, University of Gothenburg, Sahlgrenska University Hospital, Region Skåne, KTH Royal Institute of Technology, Columbia University, University College London, The University of Queensland, Institute for Molecular Bioscience, Broad Institute, Harvard University, Massachusetts General Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G1002576780, G1513236869, G1558193350, G2004031785, G2563633029, G263730981, G2697193108, G2786770482, G2909646403, G3273365655, G3918735012, G55242246, G5698529245, G583733011, G6373074959, G6406471325, Predicting, preventing and individualize treatment of heart transplanted patients, G67379338, Immunotherapeutic targeting of intratumoral MAIT cells through modulation of type-17 and type-1 signaling pathways, G7388034200, Towards precision medicine for heart failure and myocardial disease: myocardial genomics, single cell transcriptomics, and plasma profiling, LUDC-IRC för individanpassad medicin i diabetes, G804694337
OpenAlex ID: W4407184128