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Published on: January 16, 2019
Genome-wide association study of PR interval
Arne Pfeufer1, Charlotte van Noord, Kristin D Marciante
1Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. arne.pfeufer@web.de
Nature Genetics
|January 12, 2010
Summary
Genome-wide association studies identified nine genetic loci linked to the PR interval, a measure of heart electrical conduction. Five of these loci also showed associations with atrial fibrillation risk.
Area of Science:
- Cardiovascular Genetics
- Electrophysiology
- Genomics
Background:
- The PR interval on an electrocardiogram reflects atrial and atrioventricular nodal conduction.
- Disturbances in conduction are associated with an increased risk of atrial fibrillation.
Purpose of the Study:
- To identify genetic loci associated with the PR interval through a meta-analysis of genome-wide association studies.
- To investigate the overlap between genetic factors influencing PR interval and atrial fibrillation susceptibility.
Main Methods:
- Meta-analysis of genome-wide association studies (GWAS) for PR interval from seven European population-based cohorts (N = 28,517) within the CHARGE Consortium.
- Identification of significant loci associated with PR interval at P < 5 x 10(-8).
- Examination of associations between identified PR interval loci and atrial fibrillation (N = 5,741 cases).
Main Results:
- Nine genetic loci were significantly associated with the PR interval.
- Two independent associations were found at the 3p22.2 locus within voltage-gated sodium channel genes SCN10A and SCN5A.
- Six loci were located near cardiac developmental genes (e.g., NKX2-5, TBX5).
- Five loci (SCN5A, SCN10A, NKX2-5, CAV1-CAV2, SOX5) were also associated with atrial fibrillation.
Conclusions:
- Common genetic variations in ion channel and cardiac developmental genes influence atrial and atrioventricular conduction.
- These genetic factors may play a role in susceptibility to atrial fibrillation.
- The findings provide insights into the genetic underpinnings of cardiac electrical activity and arrhythmia risk.
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