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Rare Genetic Variants and Early-Onset AF in Minority Individuals
Quick Takes
- In a study of 227 probands with early-onset atrial fibrillation (AF), who were ethnic minorities, gene sequencing identified 16 probands harboring pathogenic (56%) or likely pathogenic (44%) variants.
- Most genes associated with early-onset AF (46.7%) were loss-of-function variants in the TTN gene.
Study Questions:
What is the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset atrial fibrillation (AF), and what are the genotype-phenotype associations?
Methods:
In this cohort, family-based study, probands of African and Hispanic descent with early-onset AF underwent sequencing of 60 candidate genes.
Results:
Among 227 probands, mean age was 51 years; 148 (65%) were African American, and 79 (35%) were Hispanic/Latinx. A family history of AF was verified in 24 probands with early-onset AF (10.6%). Sequencing 60 candidate genes identified 53 variants with 16 of the 227 probands harboring likely pathogenic (44%) or pathogenic (56%) variants, with most loss-of-function variants in TTN, the gene encoding the sarcomeric protein titin. Variants of unknown significance were identified in sodium channel (SCN10A), potassium channel (KCNE5), sarcomeric proteins (MYH6 and TTN), and atrial natriuretic peptide (NPPA).
Conclusions:
The authors identified likely pathogenic and pathogenic variants, with most loss-of-function variants in TTN, which increased susceptibility to early-onset AF in minority individuals.
Perspective:
Genetic understanding of AF has expanded significantly in the last two decades, but prior work has focused on the White population of European ancestry. Non-White individuals are at a lower risk of developing AF, despite a greater burden of cardiovascular risk factors. The current study identified likely pathogenic and pathogenic variants, with most loss-of-function variants in TTN, which increase susceptibility to early-onset AF in minority populations. This will allow for molecular phenotyping of AF in these populations and hopefully identify novel approaches to treatment.
Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism
Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Atrial Natriuretic Factor, Connectin, Ethnic Groups, Genetic Association Studies, Genotype, Minority Groups, Phenotype, Potassium Channels, Primary Prevention, Risk Factors, Secondary Prevention, Sodium Channels
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