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Published on: June 20, 2020
Genetic determinants of P wave duration and PR segment
Niek Verweij1, Irene Mateo Leach1, Malou van den Boogaard1
1From the Department of Cardiology (N.V., I.M.L., D.J.v.V., H.L.H., W.H.v.G., R.A.d.B., P.v.d.H.) and Department of Genetics (P.v.d.H.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Anatomy, Embryology and Physiology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (M.v.d.B., V.M.C., P.B.); and Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands (P.v.d.H.).
Genetic factors influencing the PR interval (ECG) primarily affect the PR segment, with some also impacting P wave duration. Novel genetic variants specifically linked to P wave duration were identified, offering insights into cardiac biology.
Area of Science:
- Cardiovascular Genetics
- Electrophysiology
- Genomics
Background:
- The PR interval on an electrocardiogram (ECG) reflects atrial depolarization and atrioventricular nodal delay.
- Previous genome-wide association studies (GWAS) identified genetic loci for PR interval, but their specific contributions to P wave duration or PR segment were unclear.
Purpose of the Study:
- To determine whether genetic associations with the PR interval are driven by P wave duration, PR segment, or both.
- To identify novel genetic loci associated with P wave duration and PR segment.
Main Methods:
- Replication of known PR interval loci in a European ancestry cohort.
- Genome-wide association analysis of P wave duration and PR segment separately.
- Analysis of DNA elements and gene expression in cardiac tissues (right atrium, atrioventricular node, left ventricle).
Main Results:
- Seven of nine known PR interval loci were replicated.
- Four loci were uniquely associated with the PR segment, while others were shared.
- Five novel loci were identified: KCND3 and FADS2 for P wave duration; IL17D, EFHA1, and LRCH1 for PR segment.
- Significant single-nucleotide polymorphisms were enriched in regions of active gene transcription in the right atrium.
- Genes showed significantly higher expression in the right atrium and atrioventricular node compared to the left ventricle.
Conclusions:
- Genetic associations of the PR interval are predominantly driven by genetic determinants of the PR segment.
- Some PR interval associations are reinforced by consistent effects on P wave duration.
- Novel genetic variants specifically associated with P wave duration were discovered, potentially relevant to cardiac biology.
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