Whole genome sequencing in early onset advanced heart failure

• Published in: Scientific reports Vol. 15; no. 1; pp. 4306 - 9
• Main Authors: Linnér, Erik, Czuba, Tomasz, Gidlöf, Olof, Lundgren, Jakob, Bollano, Entela, Hellberg, Maria, Celik, Selvi, Pimpalwar, Neha, Rentzsch, Philipp, Martorella, Molly, Gummesson, Anders, Melander, Olle, Albinsson, Sebastian, Dellgren, Göran, Borén, Jan, Jeppsson, Anders, Lumbers, R. Thomas, Shah, Sonia, Nilsson, Johan, Natarajan, Pradeep, Lappalainen, Tuuli, Levin, Malin, Ehrencrona, Hans, Smith, J. Gustav
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.02.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/1516; 692/4019; Adult; Age; Age of Onset; Aged; Basic Medicine; Cardiology and Cardiovascular Disease; Cardiomyopathies; Cardiomyopathy; Congestive heart failure; epidemiology; Female; Genetic Predisposition to Disease; Genetic screening; Genetic Testing; Genetics; Genomes; Genomics; Heart Failure; Heart Failure - genetics; Heart Transplantation; Humanities and Social Sciences; Humans; Ischemia; Kardiologi och kardiovaskulära sjukdomar; Literature reviews; Male; Medical and Health Sciences; Medical Genetics and Genomics (including Gene Therapy); Medicin och hälsovetenskap; Medicinsk genetik och genomik (Här ingår: Genterapi); Medicinska och farmaceutiska grundvetenskaper; methods; Middle Aged; multidisciplinary; Pathogenicity; Science; Science (multidisciplinary); Sweden; Sweden - epidemiology; Whole Genome Sequencing; Whole Genome Sequencing - methods; Sweden; Heart failure; Cardiomyopathies; Genetics; Genomics; Heart transplantation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-88465-8

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.