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Gustav Smith

Associate professor

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

Author

  • Ioanna Ntalla
  • Gustav Smith
  • Patricia B Munroe

Summary, in English

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.

Department/s

  • WCMM-Wallenberg Centre for Molecular Medicine
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Molecular Epidemiology and Cardiology

Publishing year

2020-05-21

Language

English

Publication/Series

Nature Communications

Volume

11

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Keywords

  • abnormality
  • cardiovascular system
  • disease treatment
  • electrical method
  • genetic analysis
  • heritability
  • histopathology
  • meta-analysis
  • muscle

Status

Published

Research group

  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology

ISBN/ISSN/Other

  • ISSN: 2041-1723