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)

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 Stott J, Professor David and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna
• 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 > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Communications
• Publisher: Nature Research
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
46405	1	Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.	Anna Dominiczak	British Heart Foundation (BHF)	RG/07/005/23633	RI CARDIOVASCULAR & MEDICAL SCIENCES
48357	1	Collaborative strategy for a definitive genome scan in essential hypertension: high fidelity phenotyping and "hypercontrols"	Anna Dominiczak	British Heart Foundation (BHF)	SP/08/005/25115	RI CARDIOVASCULAR & MEDICAL SCIENCES