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PR Interval Genome-Wide Association Meta-Analysis Identifies 50 Loci Associated with Atrial and Atrioventricular Electrical Activity

Citation

van Setten, Jessica; Brody, Jennifer A.; Jamshidi, Yalda; Swenson, Brenton R.; Butler, Anne M.; Campbell, Harry; Del Greco, Fabiola M.; Evans, Daniel S.; Gibson, Quince; & Gudbjartsson, Daniel F., et al. (2018). PR Interval Genome-Wide Association Meta-Analysis Identifies 50 Loci Associated with Atrial and Atrioventricular Electrical Activity. Nature Communications, 9, 2904. PMCID: PMC6060178

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.

URL

http://dx.doi.org/10.1038/s41467-018-04766-9

Reference Type

Journal Article

Year Published

2018

Journal Title

Nature Communications

Author(s)

van Setten, Jessica
Brody, Jennifer A.
Jamshidi, Yalda
Swenson, Brenton R.
Butler, Anne M.
Campbell, Harry
Del Greco, Fabiola M.
Evans, Daniel S.
Gibson, Quince
Gudbjartsson, Daniel F.
Kerr, Kathleen F.
Krijthe, Bouwe P.
Lyytikainen, Leo-Pekka
Muller, Christian
Muller-Nurasyid, Martina
Nolte, Ilja M.
Padmanabhan, Sandosh
Ritchie, Marylyn D.
Robino, Antonietta
Smith, Albert V.
Steri, Maristella
Tanaka, Toshiko
Teumer, Alexander
Trompet, Stella
Ulivi, Sheila
Verweij, Niek
Yin, Xiaoyan
Arnar, David O.
Asselbergs, Folkert W.
Bader, Joel S.
Barnard, John
Bis, Joshua C.
Blankenberg, Stefan
Boerwinkle, Eric A.
Bradford, Yuki
Buckley, Brendan M.
Chung, Mina K.
Crawford, Dana C.
den Hoed, Marcel
Denny, Josh C.
Dominiczak, Anna F.
Ehret, Georg B.
Eijgelsheim, Mark
Ellinor, Patrick T.
Felix, Stephan B.
Franco, Oscar H.
Franke, Lude
Harris, Tamara B.
Holm, Hilma
Ilaria, Gandin
Iorio, Annamaria
Kahonen, Mika
Kolcic, Ivana
Kors, Jan A.
Lakatta, Edward G.
Launer, Lenore J.
Lin, Honghuang
Lin, Henry J.
Loos, Ruth J. F.
Lubitz, Steven A.
Macfarlane, Peter W.
Magnani, Jared W.
Leach, Irene Mateo
Meitinger, Thomas
Mitchell, Braxton D.
Munzel, Thomas
Papanicolaou, George J.
Peters, Annette
Pfeufer, Arne
Pramstaller, Peter P.
Raitakari, Olli T.
Rotter, Jerome I.
Rudan, Igor
Samani, Nilesh J.
Schlessinger, David
Silva Aldana, Claudia T.
Sinner, Moritz F.
Smith, Jonathan D.
Snieder, Harold
Soliman, Elsayed Z.
Spector, Timothy D.
Stott, David J.
Strauch, Konstantin
Tarasov, Kirill V.
Thorsteinsdottir, Unnur
Uitterlinden, Andre G.
Van Wagoner, David R.
Volker, Uwe
Volzke, Henry
Waldenberger, Melanie
Westra, Harm-Jan
Wild, Philipp S.
Zeller, Tanja
Alonso, Alvaro
Avery, Christy L.
Bandinelli, Stefania
Benjamin, Emelia J.
Cucca, Francesco
Dorr, Marcus
Ferrucci, Luigi
Gasparini, Paolo
Gudnason, Vilmundur G.
Hayward, Caroline
Heckbert, Susan R.
Hicks, Andrew A.
Jukema, J. Wouter
Kaab, Stefan
Lehtimaki, Terho
Liu, Yongmei
Munroe, Patricia B.
Parsa, Afshin
Polasek, Ozren
Psaty, Bruce M.
Roden, Dan M.
Schnabel, Renate B.
Sinagra, Gianfranco
Stefansson, Kari
Stricker, Bruno H.
van der Harst, Pim
van Duijn, Cornelia M.
Wilson, James F.
Gharib, Sina A.
de Bakker, Paul I. W.
Isaacs, Aaron J.
Arking, Dan E.
Sotoodehnia, Nona

PMCID

PMC6060178