Key result
Multi-ancestry genome-wide meta-analysis identifies 210 loci linked to the PR interval.
Why the study?
The genetic basis of the electrocardiographic PR interval and its relationship to cardiac conduction and cardiovascular disease risk were incompletely understood.
Meta-Analysis (n=293,051)
Yes
Identified 210 genetic loci associated with the PR interval, highlighting the polygenic basis of cardiac conduction and its relationship with cardiovascular disease risk.
Answers are grounded in this paper and cite their sources.
Doubles explained PR-interval heritability; extends polygenic map of conduction while leaving arrhythmia risk prediction and therapy open.
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality 1,2 . We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
No takes yet. Share an insight, caveat, or question.
Ντάλλα et al. (2019) conducted a meta-analysis in Electrocardiographic PR interval (n=293,051). Genetic variants (loci) was evaluated on Genome-wide significant loci associated with PR interval (p=<5x10^-8). A multi-ancestry genome-wide association meta-analysis identified 210 loci (149 novel) associated with the PR interval, increasing the explained heritability from 33.5% to 62.6%.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: