Why the study?
The electrocardiographic PR interval reflects atrioventricular conduction and is associated with conduction abnormalities, pacemaker implantation, AF, and cardiovascular mortality, but its full genetic architecture was incompletely understood.
Identified 210 genetic loci associated with PR interval duration, highlighting key regulatory processes for atrioventricular conduction and linking polygenic predisposition to cardiovascular disease risk.
Answers are grounded in this paper and cite their sources.
Supports polygenic PR risk as an AF and conduction disease endophenotype but should not yet change practice; extends AV conduction genetics.
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.
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Ντάλλα et al. (2019) studied this question.
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