000131441 001__ 131441
000131441 005__ 20240319080946.0
000131441 0247_ $$2doi$$a10.1038/s41467-022-32821-z
000131441 0248_ $$2sideral$$a136848
000131441 037__ $$aART-2022-136848
000131441 041__ $$aeng
000131441 100__ $$aYoung, William J.
000131441 245__ $$aGenetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
000131441 260__ $$c2022
000131441 5203_ $$aThe 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.
000131441 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000131441 590__ $$a16.6$$b2022
000131441 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 73 = 0.082$$c2022$$dQ1$$eT1
000131441 592__ $$a5.116$$b2022
000131441 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1
000131441 593__ $$aPhysics and Astronomy (miscellaneous)$$c2022$$dQ1
000131441 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1
000131441 594__ $$a24.9$$b2022
000131441 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131441 700__ $$aLahrouchi, Najim
000131441 700__ $$aIsaacs, Aaron
000131441 700__ $$aDuong, ThuyVy
000131441 700__ $$aFoco, Luisa
000131441 700__ $$aAhmed, Farah
000131441 700__ $$aBrody, Jennifer A.
000131441 700__ $$aSalman, Reem
000131441 700__ $$aNoordam, Raymond
000131441 700__ $$aBenjamins, Jan-Walter
000131441 700__ $$aHaessler, Jeffrey
000131441 700__ $$aLyytikäinen, Leo-Pekka
000131441 700__ $$aRepetto, Linda
000131441 700__ $$aConcas, Maria Pina
000131441 700__ $$0(orcid)0000-0003-4130-5866$$aRamírez, J.$$uUniversidad de Zaragoza
000131441 700__ $$a[et al.]
000131441 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000131441 773__ $$g13, 1 (2022)$$tNature communications$$x2041-1723
000131441 8564_ $$s3861504$$uhttps://zaguan.unizar.es/record/131441/files/texto_completo.pdf$$yVersión publicada
000131441 8564_ $$s2670154$$uhttps://zaguan.unizar.es/record/131441/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131441 909CO $$ooai:zaguan.unizar.es:131441$$particulos$$pdriver
000131441 951__ $$a2024-03-18-12:33:53
000131441 980__ $$aARTICLE