Gustav Smith
Associate professor
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
Author
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