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

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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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Springer Nature
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Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide 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 overrepresented 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 similar to 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, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Common variants , Heart-rate , QRS duration , Cardiac conduction , Fibrillation , Epidemiology , Cohorts , Risk , Rare , SNPs
van Setten, J. and Brody, J. A. and Jamshidi, Y. and Swenson, B. R. and Butler, A. M. and Campbell, H. and Del Greco, F. M. and Evans, D. S. and Gibson, Q. and Gudbjartsson, D. F. and Kerr, K. F. and Krijthe, B. P. and Lyytikäinen, L.-P. and Müller, C. and Müller-Nurasyid, M. and Nolte, I. M. and Padmanabhan, S. and Ritchie, M. D. and Robino, A. and Smith, A. V. and Steri, M. and Tanaka, T. and Teumer, A. and Trompet, S. and Ulivi, S. and Verweij, N. and Yin, X. and Arnar, D. O. and Asselbergs, F. W. and Bader, J. S. and Barnard, J. and Bis, J. and Blankenberg, S. and Boerwinkle, E. and Bradford, Y. and Buckley, B. M. and Chung, M. K. and Crawford, D. and den Hoed, M. and Denny, J. C. and Dominiczak, A. F. and Ehret, G. B. and Eijgelsheim, M. and Ellinor, P. T. and Felix, S. B. and Franco, O. H. and Franke, L. and Harris, T. B. and Holm, H. and Ilaria, G. and Iorio, A. and Kähönen, M. and Kolcic, I. and Kors, J. A. and Lakatta, E. G. and Launer, L. J. and Lin, H. and Lin, H. J. and Loos, R. J. F. and Lubitz, S. A. and Macfarlane, P. W. and Magnani, J. W. and Leach, I. M. and Meitinger, T. and Mitchell, B. D. and Munzel, T. and Papanicolaou, G. J. and Peters, A. and Pfeufer, A. and Pramstaller, P. P. and Raitakari, O. T. and Rotter, J. I. and Rudan, I. and Samani, N. J. and Schlessinger, D. and Silva Aldana, C. T. and Sinner, M. F. and Smith, J. D. and Snieder, H. and Soliman, E. Z. and Spector, T. D. and Stott, D. J. and Strauch, K. and Tarasov, K. V. and Thorsteinsdottir, U. and Uitterlinden, A. G. and Van Wagoner, D. R. and Völker, U. and Völzke, H. and Waldenberger, M. and Jan Westra, H. and Wild, P. S. and Zeller, T. and Alonso, A. and Avery, C. L. and Bandinelli, S. and Benjamin, E. J. and Cucca, F. and Dörr, M. and Ferrucci, L. and Gasparini, P. and Gudnason, V. and Hayward, C. and Heckbert, S. R. and Hicks, A. A. and Jukema, J. W. and Kääb, S. and Lehtimäki, T. and Liu, Y. and Munroe, P. B. and Parsa, A. and Polasek, O. and Psaty, B. M. and Roden, D. M. and Schnabel, R. B. and Sinagra, G. and Stefansson, K. and Stricker, B. H. and van der Harst, P. and van Duijn, C. M. and Wilson, J. F. and Gharib, S. A. and de Bakker, P. I. W. and Isaacs, A. and Arking, D. E. and Sotoodehnia, N. (2018) 'PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity', Nature Communications, 9(1), 2904 (11pp). doi: 10.1038/s41467-018-04766-9