Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Research output: Contribution to journalArticle

Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

Details

Authors
Organisations
External organisations
  • National Institute for Health Research, United Kingdom
  • Skåne University Hospital
  • Queen Mary University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Keywords

  • abnormality, cardiovascular system, disease treatment, electrical method, genetic analysis, heritability, histopathology, meta-analysis, muscle
Original languageEnglish
Article number2542
JournalNature Communications
Volume11
Publication statusPublished - 2020 May 21
Publication categoryResearch
Peer-reviewedYes