van Setten, J;
Brody, JA;
Jamshidi, Y;
Swenson, BR;
Butler, AM;
Campbell, H;
Del Greco, FM;
Evans, DS;
Gibson, Q;
Gudbjartsson, DF;
et al.
van Setten, J; Brody, JA; Jamshidi, Y; Swenson, BR; Butler, AM; Campbell, H; Del Greco, FM; Evans, DS; Gibson, Q; Gudbjartsson, DF; Kerr, KF; Krijthe, BP; Lyytikäinen, L-P; Müller, C; Müller-Nurasyid, M; Nolte, IM; Padmanabhan, S; Ritchie, MD; Robino, A; Smith, AV; Steri, M; Tanaka, T; Teumer, A; Trompet, S; Ulivi, S; Verweij, N; Yin, X; Arnar, DO; Asselbergs, FW; Bader, JS; Barnard, J; Bis, J; Blankenberg, S; Boerwinkle, E; Bradford, Y; Buckley, BM; Chung, MK; Crawford, D; den Hoed, M; Denny, JC; Dominiczak, AF; Ehret, GB; Eijgelsheim, M; Ellinor, PT; Felix, SB; Franco, OH; Franke, L; Harris, TB; Holm, H; Ilaria, G; Iorio, A; Kähönen, M; Kolcic, I; Kors, JA; Lakatta, EG; Launer, LJ; Lin, H; Lin, HJ; Loos, RJF; Lubitz, SA; Macfarlane, PW; Magnani, JW; Leach, IM; Meitinger, T; Mitchell, BD; Munzel, T; Papanicolaou, GJ; Peters, A; Pfeufer, A; Pramstaller, PP; Raitakari, OT; Rotter, JI; Rudan, I; Samani, NJ; Schlessinger, D; Silva Aldana, CT; Sinner, MF; Smith, JD; Snieder, H; Soliman, EZ; Spector, TD; Stott, DJ; Strauch, K; Tarasov, KV; Thorsteinsdottir, U; Uitterlinden, AG; Van Wagoner, DR; Völker, U; Völzke, H; Waldenberger, M; Jan Westra, H; Wild, PS; Zeller, T; Alonso, A; Avery, CL; Bandinelli, S; Benjamin, EJ; Cucca, F; Dörr, M; Ferrucci, L; Gasparini, P; Gudnason, V; Hayward, C; Heckbert, SR; Hicks, AA; Jukema, JW; Kääb, S; Lehtimäki, T; Liu, Y; Munroe, PB; Parsa, A; Polasek, O; Psaty, BM; Roden, DM; Schnabel, RB; Sinagra, G; Stefansson, K; Stricker, BH; van der Harst, P; van Duijn, CM; Wilson, JF; Gharib, SA; de Bakker, PIW; Isaacs, A; Arking, DE; Sotoodehnia, N
(2018)
PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.
Nat Commun, 9 (1).
p. 2904.
ISSN 2041-1723
https://doi.org/10.1038/s41467-018-04766-9
SGUL Authors: Jamshidi, Yalda
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: |
Article
|
| Additional Information: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018 |
| Keywords: |
MD Multidisciplinary |
| SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
| Journal or Publication Title: |
Nat Commun |
| ISSN: |
2041-1723 |
| Language: |
eng |
| Dates: |
| Date | Event |
|---|
| 25 July 2018 | Published | | 21 May 2018 | Accepted |
|
| Publisher License: |
Creative Commons: Attribution 4.0 |
| Projects: |
|
| PubMed ID: |
30046033 |
| Web of Science ID: |
WOS:000439687600002 |
 |
Go to PubMed abstract |
| URI: |
https://openaccess.sgul.ac.uk/id/eprint/110049 |
| Publisher's version: |
https://doi.org/10.1038/s41467-018-04766-9 |
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