Genome-Wide Association Study of Accessory Atrioventricular Pathways

Area of Science:

• Cardiovascular Genetics
• Electrophysiology
• Genomics

Background:

• Genetic underpinnings of accessory atrioventricular pathways (APs) and associated arrhythmias remain poorly understood.
• Identifying genetic factors is crucial for understanding disease mechanisms and developing targeted therapies.

Purpose of the Study:

• To investigate the genetic basis of accessory atrioventricular pathways (APs) and their associated arrhythmias using a genome-wide association study (GWAS).

Main Methods:

• A large-scale GWAS was conducted on individuals with APs, defined by ICD codes or electrophysiology (EP) confirmation.
• Genome-wide significant variants were tested for association with AP-affiliated arrhythmias (PSVT, AF) and cardiac physiology measures.
• Multi-national cohorts from Iceland, Denmark, the US, and the UK were included, with data spanning from 1983 to 2022.

Main Results:

• Three common missense variants in CCDC141 and SCN10A were significantly associated with APs.
• These variants also showed associations with paroxysmal supraventricular tachycardia (PSVT) and atrial fibrillation (AF), confirming their role in AP-affiliated arrhythmias.
• AP risk alleles correlated with higher heart rate and shorter PR interval, suggesting a role in cardiac conduction and chronotropic response.

Conclusions:

• Sequence variants in CCDC141 and SCN10A are associated with APs and influence the risk of related arrhythmias like PSVT and AF.
• Genetic variations affecting heart rate modulation and atrioventricular conduction may contribute to AP-affiliated arrhythmias.
• Further research into CCDC141 could offer novel therapeutic targets for managing APs and related arrhythmias.