Genetic Determinants of P Wave Duration and PR Segment
Background—The PR interval on the electrocardiogram reflects atrial depolarization and AV nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. GWAS have identified a number of genetic loci for PR interval but it remains to be determined whether this is driven by P wave duration, PR segment or both.
Methods and Results—We replicated 7 of the 9 known PR interval loci in 16,468 individuals of European ancestry. Four loci were unambiguously associated with PR segment while the others were shared for P wave duration and PR segment. Next, we performed a genome-wide analysis on P wave duration and PR segment separately and identified five novel loci. SNPs in KCND3 (P=8.3×10-11) and FADS2 (P=2.7×10-8) were associated with P wave duration, whereas SNPs near IL17D (P=2.3×10-8), in EFHA1 (P=3.3×10-10) and LRCH1 (P=2.1×10-8) were associated with PR segment. Analysis on DNA elements indicated that genome-wide significant SNPs were enriched at genomic regions suggesting active gene transcription in the human right atrium. Quantitative-PCR showed that genes were significantly higher expressed in the right atrium and AV-node compared to left ventricle (P=5.6×10-6).
Conclusions—Genetic associations of PR interval appear to be mainly driven by genetic determinants of the PR segment. Some of the PR interval associations are strengthened by a directional consistent effect of genetic determinants of P wave duration. Through genome-wide association we also identified genetic variants specifically associated with P wave duration which might be relevant for cardiac biology.
- Received October 10, 2013.
- Revision received April 8, 2014.
- Accepted April 16, 2014.