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Young, W.J.* ; Lahrouchi, N.* ; Isaacs, A.* ; Duong, T.V.* ; Foco, L.* ; Ahmed, F.* ; Brody, J.A.* ; Salman, R.* ; Noordam, R.* ; Benjamins, J.W.* ; Haessler, J.* ; Lyytikäinen, L.P.* ; Repetto, L.* ; Concas, M.P.* ; van den Berg, M.E.* ; Weiss, S.* ; Baldassari, A.R.* ; Bartz, T.M.* ; Cook, J.P.* ; Evans, D.S.* ; Freudling, R. ; Hines, O.* ; Isaksen, J.L.* ; Lin, H.* ; Mei, H.* ; Moscati, A.* ; Müller-Nurasyid, M. ; Nursyifa, C.* ; Qian, Y.* ; Richmond, A.* ; Roselli, C.* ; Ryan, K.A.* ; Tarazona-Santos, E.* ; Thériault, S.* ; Van Duijvenboden, S.* ; Warren, H.R.* ; Yao, J.* ; Raza, D.* ; Aeschbacher, S.* ; Ahlberg, G.* ; Alonso, A.* ; Andreasen, L.* ; Bis, J.C.* ; Boerwinkle, E.* ; Campbell, A.* ; Catamo, E.* ; Cocca, M.* ; Cutler, M.J.* ; Darbar, D.* ; de Grandi, A.* ; de Luca, A.* ; Ding, J.* ; Ellervik, C.* ; Ellinor, P.T.* ; Felix, S.B.* ; Froguel, P.* ; Fuchsberger, C.* ; Gögele, M.* ; Graff, C.* ; Graff, M.* ; Guo, X.* ; Hansen, T.* ; Heckbert, S.R.* ; Huang, P.L.* ; Huikuri, H.V.* ; Hutri-Kähönen, N.* ; Ikram, M.A.* ; Jackson, R.D.* ; Junttila, J.* ; Kavousi, M.* ; Kors, J.A.* ; Leal, T.P.* ; Lemaitre, R.N.* ; Lin, H.J.* ; Lind, L.* ; Linneberg, A.* ; Liu, S.* ; Macfarlane, P.W.* ; Mangino, M.* ; Mezzavilla, M.* ; Mishra, P.P.* ; Mitchell, R.N.* ; Mononen, N.* ; Montasser, M.E.* ; Morrison, A.C.* ; Nauck, M.* ; Nauffal, V.* ; Navarro, P.* ; Nikus, K.* ; Paré, G.* ; Patton, K.K.* ; Pelliccione, G.* ; Pittman, A.* ; Porteous, D.J.* ; Pramstaller, P.P.* ; Preuss, M.H.* ; Raitakari, O.T.* ; Reiner, A.P.* ; Ribeiro, A.L.P.* ; Rice, C.M.* ; Risch, L.* ; Schlessinger, D.* ; Schotten, U.* ; Schurmann, C.* ; Shen, X.* ; Shoemaker, M.B.* ; Sinagra, G.* ; Sinner, M.F.* ; Soliman, E.Z.* ; Stoll, M.* ; Strauch, K. ; Tarasov, K.V.* ; Taylor, K.D.* ; Tinker, A.* ; Trompet, S.* ; Uitterlinden, A.* ; Völker, U.* ; Völzke, H.* ; Waldenberger, M. ; Conen, D.* ; Correa, A.* ; Cucca, F.* ; Dörr, M.* ; Kooperberg, C.* ; Mook-Kanamori, D.O.* ; Morris, A.P.* ; Orini, M.* ; Padmanabhan, S.* ; Pattaro, C.* ; Peters, A. ; Psaty, B.M.* ; Rotter, J.I.* ; Stricker, B.* ; van der Harst, P.* ; van Duijn, C.M.* ; Verweij, N.* ; Wilson, J.F.* ; Arking, D.E.* ; Ramirez, J.* ; Sotoodehnia, N.* ; Mifsud, B.* ; Newton-Cheh, C.* ; Munroe, P.B.*

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

Nat. Commun. 13:5144 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 13, Issue: 1, Pages: , Article Number: 5144 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-504091-001
G-504000-010
DOI 10.1038/s41467-022-32821-z
WOS ID WOS:000848744900005
Scopus ID 85137092502
PubMed ID 36050321
Erfassungsdatum 2022-10-19
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