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

TitleMulti-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.
Publication TypeJournal Article
Year of Publication2020
AuthorsNtalla I, Weng L-C, Cartwright JH, et al.
Secondary AuthorsMunroe PB
JournalNat Commun
Date Published2020 05 21
KeywordsArrhythmias, Cardiac, Cardiovascular Diseases, Electrocardiography, Endophenotypes, Female, Gene Expression, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Quantitative Trait Loci

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.

Alternate JournalNat Commun
PubMed ID32439900
PubMed Central IDPMC7242331
Grant ListR01 HL139731 / HL / NHLBI NIH HHS / United States