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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

TitlePR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.
Publication TypeJournal Article
Year of Publication2018
Authorsvan Setten J, Brody JA, Jamshidi Y, et al.
Secondary AuthorsSotoodehnia N
JournalNat Commun
Volume9
Issue1
Pagination2904
Date Published2018 07 25
ISSN2041-1723
KeywordsAtrial Function, Atrioventricular Node, Electrocardiography, Electrophysiological Phenomena, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Risk Factors
Abstract

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

DOI10.1038/s41467-018-04766-9
Alternate JournalNat Commun
PubMed ID30046033
PubMed Central IDPMC6060178
Grant ListR01 HL139731 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL111314 / HL / NHLBI NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
K23 HL114724 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States