Rudaka, IrinaVilne, BaibaIsakova, JekaterinaKalejs, OskarsGailite, LindaRots, Dmitrijs2023-06-072023-06-072023-03Rudaka, I, Vilne, B, Isakova, J, Kalejs, O, Gailite, L & Rots, D 2023, 'Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors', Journal of Cardiovascular Development and Disease, vol. 10, no. 3, 104. https://doi.org/10.3390/jcdd100301042308-3425Mendeley: baa8097a-a838-32bd-a70e-cfd6af1ecd0fhttps://dspace.rsu.lv/jspui/handle/123456789/12318Funding Information: This research was funded by the Latvian Council of Science, project, “The role of clonal hemato-poiesis of indeterminate potential as a potential driver of cardiovascular diseases and its associ-ation with clinical outcome”, project No. lzp-2021/1-0293. Publisher Copyright: © 2023 by the authors.Background: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. Aims: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. Materials and Methods: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Results: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population—c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. Conclusions: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.273416enginfo:eu-repo/semantics/openAccessearly-onset atrial fibrillationgeneticsnext-generation sequencingpathogenic variants3.1 Basic medicine1.1. Scientific article indexed in Web of Science and/or Scopus databasePharmacology, Toxicology and Pharmaceutics(all)Pharmacology (medical)/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.3390/jcdd10030104http://www.scopus.com/inward/record.url?scp=85151093413&partnerID=8YFLogxKhttps://www.mendeley.com/catalogue/baa8097a-a838-32bd-a70e-cfd6af1ecd0f/