000145085 001__ 145085
000145085 005__ 20260112133341.0
000145085 0247_ $$2doi$$a10.1161/JAHA.123.034760
000145085 0248_ $$2sideral$$a139902
000145085 037__ $$aART-2024-139902
000145085 041__ $$aeng
000145085 100__ $$aYoung, William J.
000145085 245__ $$aGenome-wide interaction analyses of serum calcium on ventricular repolarization time in 125393 participants
000145085 260__ $$c2024
000145085 5060_ $$aAccess copy available to the general public$$fUnrestricted
000145085 5203_ $$aBackground
Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome‐wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability.
Methods and Results
We performed genome‐wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2‐stage analysis (genome‐wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single‐stage genome‐wide meta‐analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2‐degrees of freedom joint main and interaction and 1‐degree of freedom interaction P values. In 2‐stage and single‐stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2‐degrees of freedom joint main and interaction P value <5×10−8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single‐stage meta‐analysis were not reported previously (SPPL2B and RFX6).
Conclusions
We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.
000145085 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2021-128972OA-I00$$9info:eu-repo/grantAgreement/EC/H2020/786833/EU/GENetics and the Electrocardiogram for predicting Scd rISk/GENESIS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 786833-GENESIS
000145085 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000145085 590__ $$a5.3$$b2024
000145085 592__ $$a2.189$$b2024
000145085 591__ $$aCARDIAC & CARDIOVASCULAR SYSTEMS$$b41 / 230 = 0.178$$c2024$$dQ1$$eT1
000145085 593__ $$aCardiology and Cardiovascular Medicine$$c2024$$dQ1
000145085 594__ $$a8.5$$b2024
000145085 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000145085 700__ $$avan der Most, Peter J.
000145085 700__ $$aBartz, Traci M.
000145085 700__ $$aBos, Maxime M.
000145085 700__ $$aBiino, Ginevra
000145085 700__ $$aDuong, ThuyVy
000145085 700__ $$aFoco, Luisa
000145085 700__ $$aLominchar, Jesus T.
000145085 700__ $$aMüller-Nurasyid, Martina
000145085 700__ $$aNardone, Giuseppe Giovanni
000145085 700__ $$aPecori, Alessandro
000145085 700__ $$0(orcid)0000-0003-4130-5866$$aRamirez, Julia$$uUniversidad de Zaragoza
000145085 700__ $$aRepetto, Linda
000145085 700__ $$aSchramm, Katharina
000145085 700__ $$aShen, Xia
000145085 700__ $$avan Duijvenboden, Stefan
000145085 700__ $$avan Heemst, Diana
000145085 700__ $$aWeiss, Stefan
000145085 700__ $$aYao, Jie
000145085 700__ $$aBenjamins, Jan-Walter
000145085 700__ $$aAlonso, Alvaro
000145085 700__ $$aSpedicati, Beatrice
000145085 700__ $$aBiggs, Mary L.
000145085 700__ $$aBrody, Jennifer A.
000145085 700__ $$aDörr, Marcus
000145085 700__ $$aFuchsberger, Christian
000145085 700__ $$aGögele, Martin
000145085 700__ $$aGuo, Xiuqing
000145085 700__ $$aIkram, M. Arfan
000145085 700__ $$aJukema, J. Wouter
000145085 700__ $$aKääb, Stefan
000145085 700__ $$aKanters, Jørgen K.
000145085 700__ $$aLin, Henry J.
000145085 700__ $$aLinneberg, Allan
000145085 700__ $$aNauck, Matthias
000145085 700__ $$aNolte, Ilja M.
000145085 700__ $$aPianigiani, Giulia
000145085 700__ $$aSantin, Aurora
000145085 700__ $$aSoliman, Elsayed Z.
000145085 700__ $$aTesolin, Paola
000145085 700__ $$aVaccargiu, Simona
000145085 700__ $$aWaldenberger, Melanie
000145085 700__ $$avan der Harst, Pim
000145085 700__ $$aVerweij, Niek
000145085 700__ $$aArking, Dan E.
000145085 700__ $$aConcas, Maria Pina
000145085 700__ $$aDe Grandi, Alessandro
000145085 700__ $$aGirotto, Giorgia
000145085 700__ $$aGrarup, Niels
000145085 700__ $$aKavousi, Maryam
000145085 700__ $$aMook-Kanamori, Dennis O.
000145085 700__ $$aNavarro, Pau
000145085 700__ $$aOrini, Michele
000145085 700__ $$aPadmanabhan, Sandosh
000145085 700__ $$aPattaro, Cristian
000145085 700__ $$aPeters, Annette
000145085 700__ $$aPirastu, Mario
000145085 700__ $$aPramstaller, Peter P.
000145085 700__ $$aHeckbert, Susan R.
000145085 700__ $$aSinner, Mortiz
000145085 700__ $$aSnieder, Harold
000145085 700__ $$aVölker, Uwe
000145085 700__ $$aWilson, James F.
000145085 700__ $$aGauderman, W. James
000145085 700__ $$aLambiase, Pier D.
000145085 700__ $$aSotoodehnia, Nona
000145085 700__ $$aTinker, Andrew
000145085 700__ $$aWarren, Helen R.
000145085 700__ $$aNoordam, Raymond
000145085 700__ $$aMunroe, Patricia B.
000145085 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000145085 773__ $$g13, 17 (2024), e034760. 16 pp.]$$tJournal of the American Heart Association. Cardiovascular and cerebrovascular disease$$x2047-9980
000145085 8564_ $$s19480807$$uhttps://zaguan.unizar.es/record/145085/files/texto_completo.pdf$$yVersión publicada
000145085 8564_ $$s3023405$$uhttps://zaguan.unizar.es/record/145085/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000145085 909CO $$ooai:zaguan.unizar.es:145085$$particulos$$pdriver
000145085 951__ $$a2026-01-12-13:14:33
000145085 980__ $$aARTICLE