Application of next generation sequencing in cardiology: current and future precision medicine implications

Eirini Papadopoulou; Dimitra Bouzarelou; George Tsaousis; Athanasios Papathanasiou; Georgia Vogiatzi; Charalambos Vlachopoulos; Antigoni Miliou; Panagiota Papachristou; Efstathia Prappa; Georgios Servos; Konstantinos Ritsatos; Aristeidis Seretis; Alexandra Frogoudaki; George Nasioulas

doi:10.3389/fcvm.2023.1202381

Application of next generation sequencing in cardiology: current and future precision medicine implications

Front Cardiovasc Med. 2023 Jun 23:10:1202381. doi: 10.3389/fcvm.2023.1202381. eCollection 2023.

Authors

Affiliations

¹ Genekor Medical S.A., Athens, Greece.
² Third Department of Cardiology, Sotiria Hospital, Athens, Greece.
³ Unit of Inherited Cardiac Conditions and Sports Cardiology, First Department of Cardiology, National and Kapodistrian University of Athens, Athens, Greece.
⁴ Cardiology Department, "P. & A. Kyriakou" Children's Hospital, Athens, Greece.
⁵ Second Department of Cardiology, Arrhythmia Unit, Evangelismos General Hospital of Athens, Athens, Greece.
⁶ Pediatric Cardiology Unit, "P. & A. Kyriakou" Children's Hospital, Athens, Greece.
⁷ Unit of Inherited and Rare Cardiovascular Diseases, Onassis Cardiac Surgery Center, Athens, Greece.
⁸ Second Department of Cardiology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed.

Keywords: cardiogenetics; cardiovascular diseases; genetic analysis; next generation sequencing; personalized treatment.

Publication types

Review