000148280 001__ 148280
000148280 005__ 20250115160155.0
000148280 0247_ $$2doi$$a10.1161/CIRCGEN.120.003231
000148280 0248_ $$2sideral$$a136854
000148280 037__ $$aART-2021-136854
000148280 041__ $$aeng
000148280 100__ $$aYoung, William J.
000148280 245__ $$aGenetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank
000148280 260__ $$c2021
000148280 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148280 5203_ $$aBackground:
ECG markers of ventricular depolarization and repolarization are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian randomization (MR).
Methods:
Independent lead variants from a newly performed genome-wide association study for serum calcium in >300 000 European-ancestry participants from UK Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT, and QRS intervals using an inverse-weighted method in 76 226 participants not contributing to the serum calcium genome-wide association study. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR pleiotropy residual sum and outlier were performed to test for the presence of horizontal pleiotropy.
Results:
Two hundred five independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01 ms [95% CI, 2.03 to 3.99]) and JT (2.89 ms [1.91 to 3.87]) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses.
Conclusions:
These analyses support a causal effect of serum calcium levels on ventricular repolarization, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may, therefore, directly influence cardiovascular disease risk.
000148280 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000148280 590__ $$a7.465$$b2021
000148280 591__ $$aGENETICS & HEREDITY$$b17 / 175 = 0.097$$c2021$$dQ1$$eT1
000148280 591__ $$aCARDIAC & CARDIOVASCULAR SYSTEMS$$b30 / 143 = 0.21$$c2021$$dQ1$$eT1
000148280 592__ $$a2.444$$b2021
000148280 593__ $$aGenetics$$c2021$$dQ1
000148280 593__ $$aCardiology and Cardiovascular Medicine$$c2021$$dQ1
000148280 594__ $$a11.8$$b2021
000148280 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000148280 700__ $$aWarren, Helen R.
000148280 700__ $$aMook-Kanamori, Dennis O.
000148280 700__ $$0(orcid)0000-0003-4130-5866$$aRamírez, Julia
000148280 700__ $$avan Duijvenboden, Stefan
000148280 700__ $$aOrini, Michele
000148280 700__ $$aTinker, Andrew
000148280 700__ $$avan Heemst, Diana
000148280 700__ $$aLambiase, Pier D.
000148280 700__ $$aJukema, J. Wouter
000148280 700__ $$aMunroe, Patricia B.
000148280 700__ $$aNoordam, Raymond
000148280 773__ $$g14, 3 (2021), 331-338$$pCirc., Genom. precis. med.$$tCirculation. Genomic and precision medicine$$x2574-8300
000148280 8564_ $$s792998$$uhttps://zaguan.unizar.es/record/148280/files/texto_completo.pdf$$yVersión publicada
000148280 8564_ $$s2509400$$uhttps://zaguan.unizar.es/record/148280/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000148280 909CO $$ooai:zaguan.unizar.es:148280$$particulos$$pdriver
000148280 951__ $$a2025-01-15-15:06:25
000148280 980__ $$aARTICLE