PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Publication date
2018-12-01
Authors
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.
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Document Type
Article
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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.
Keywords
General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy
Citation
van Setten, J, Brody, J A, Jamshidi, Y, Swenson, B R, Butler, A M, Campbell, H, Del Greco, F M, Evans, D S, Gibson, Q, Gudbjartsson, D F, Kerr, K F, Krijthe, B P, Lyytikäinen, L P, Müller, C, Müller-Nurasyid, M, Nolte, I M, Padmanabhan, S, Ritchie, M D, Robino, A, Smith, A V, Steri, M, Tanaka, T, Teumer, A, Trompet, S, Ulivi, S, Verweij, N, Yin, X, Arnar, D O, Asselbergs, F W, Bader, J S, Barnard, J, Bis, J, Blankenberg, S, Boerwinkle, E, Bradford, Y, Buckley, B M, Chung, M K, Crawford, D, den Hoed, M, Denny, J C, Dominiczak, A F, Ehret, G B, Eijgelsheim, M, Ellinor, P T, Felix, S B, Franco, O H, Franke, L, Harris, T B, Holm, H, Ilaria, G, Iorio, A, Kähönen, M, Kolcic, I, Kors, J A, Lakatta, E G, Launer, L J, Lin, H, Lin, H J, Loos, R J F, Lubitz, S A, Macfarlane, P W, Magnani, J W, Leach, I M, Meitinger, T, Mitchell, B D, Munzel, T, Papanicolaou, G J, Peters, A, Pfeufer, A, Pramstaller, P P, Raitakari, O T, Rotter, J I, Rudan, I, Samani, N J, Schlessinger, D, Silva Aldana, C T, Sinner, M F, Smith, J D, Snieder, H, Soliman, E Z, Spector, T D, Stott, D J, Strauch, K, Tarasov, K V, Thorsteinsdottir, U, Uitterlinden, A G, Van Wagoner, D R, Völker, U, Völzke, H, Waldenberger, M, Jan Westra, H, Wild, P S, Zeller, T, Alonso, A, Avery, C L, Bandinelli, S, Benjamin, E J, Cucca, F, Dörr, M, Ferrucci, L, Gasparini, P, Gudnason, V, Hayward, C, Heckbert, S R, Hicks, A A, Jukema, J W, Kääb, S, Lehtimäki, T, Liu, Y, Munroe, P B, Parsa, A, Polasek, O, Psaty, B M, Roden, D M, Schnabel, R B, Sinagra, G, Stefansson, K, Stricker, B H, van der Harst, P, van Duijn, C M, Wilson, J F, Gharib, S A, de Bakker, P I W, Isaacs, A, Arking, D E & Sotoodehnia, N 2018, 'PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity', Nature Communications, vol. 9, no. 1, 2904. https://doi.org/10.1038/s41467-018-04766-9