Abstract
Sudden cardiac death (SCD) is defined by the World Health Organization (WHO) as death within 1 h of symptom onset (witnessed) or within 24 h of being observed alive and symptom free (unwitnessed). It affects more than 3 million people annually worldwide and affects approximately 1/1000 people each year in the USA. Familial studies of syndromes with Mendelian inheritance, candidate genes analyses, and genome-wide association studies (GWAS) have helped our understanding of the genetics of SCD. We will review the genetics of arrhythmogenic hereditary syndromes with Mendelian inheritance from familial studies with structural heart disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) as well as primary electrical causes (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome). In addition, we will review the genetics of intermediate phenotypes for SCD such as coronary artery disease and electrocardiographic variables (QT interval, QRS duration, and RR interval). Finally, we will review rare and common variants that are associated with SCD in the general population and were identified from candidate gene analyses and GWAS. Our understanding of the genetics of SCD will improve by the use of next-generation sequencing/whole-exome sequencing as well as whole-genome sequencing which have the potential to discover unsuspected common and rare genetic variants that might be associated with SCD.
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Marwan M. Refaat, Mostafa Hotait, and Barry London declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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This article is part of the Topical Collection on Invasive Electrophysiology and Pacing
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Refaat, M.M., Hotait, M. & London, B. Genetics of Sudden Cardiac Death. Curr Cardiol Rep 17, 53 (2015). https://doi.org/10.1007/s11886-015-0606-8
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DOI: https://doi.org/10.1007/s11886-015-0606-8
Keywords
- Sudden cardiac death
- Arrhythmogenic hereditary syndromes
- Genetics
- Genome-wide association studies
- Cardiomyopathies
- Hypertrophic cardiomyopathy
- Dilated cardiomyopathy
- Arrhythmogenic right ventricular cardiomyopathy/dysplasia
- Long QT syndrome
- Short QT syndrome
- Brugada syndrome
- Catecholaminergic polymorphic ventricular tachycardia