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

Van Setten, J. et al. (2018) PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity. Nature Communications, 9, 2904. (doi:10.1038/s41467-018-04766-9) (PMID:30046033) (PMCID:PMC6060178)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and Stott J, Professor David
Authors: Van Setten, J., Brody, J. A., Jamshidi, Y., R. Swenson, B., Butler, A. M., Campbell, H., Del Greco M., F., Evans, D. S., Gibson, Q., Gudbjartsson, D. F., F. Kerr, K., 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., anaka, T. 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., 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., Lorio, 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., Westra, H. J., Wild, P. S., Zeller, T., Alonso, A., Avery, C. L., Bandinelli, S., Benjam, 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., and Sotoodehnia, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 2904
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
464051Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.Anna DominiczakBritish Heart Foundation (BHF)RG/07/005/23633RI CARDIOVASCULAR & MEDICAL SCIENCES
483571Collaborative strategy for a definitive genome scan in essential hypertension: high fidelity phenotyping and "hypercontrols"Anna DominiczakBritish Heart Foundation (BHF)SP/08/005/25115RI CARDIOVASCULAR & MEDICAL SCIENCES