Evidence map›Paper›PMID 33887147›Full record

Trial reportCirculation. Genomic and precision medicine2021

Genetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank.

William J Young, Helen R Warren, Dennis O Mook-Kanamori, Julia Ramírez, Stefan van Duijvenboden, Michele Orini, Andrew Tinker, Diana van Heemst, Pier D Lambiase, J Wouter Jukema and 2 more

Open access · hybridAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Genomic and precision medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 3 syntheses or guidelines pooled it, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

William J YoungClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Helen R WarrenClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology (D.O.M.-K.), Leiden University Medical Center, the Netherlands.
Julia RamírezClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Stefan van DuijvenbodenClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Michele OriniBarts Heart Centre, St Bartholomew's Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.).
Andrew TinkerClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Diana van HeemstDepartment of Internal Medicine (D.v.H., R.N.), Leiden University Medical Center, the Netherlands.
Pier D LambiaseBarts Heart Centre, St Bartholomew's Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.).
J Wouter JukemaDepartment of Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands.
Patricia B MunroeClinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London.
Raymond NoordamDepartment of Internal Medicine (D.v.H., R.N.), Leiden University Medical Center, the Netherlands.
Queen Mary University of London · GBLeiden University Medical Center · NLSt Bartholomew's Hospital · GB

Funding

British Heart Foundation FS/16/30/32162Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/N025083/1Medical Research Council MR/R017468/1
6 · The paper itself

Abstract

backgroundECG 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).

methodsIndependent 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.

resultsTwo 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.

conclusionsThese 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.

Indexed as

ElectrocardiographyAgedCalciumFemaleHumansLong QT SyndromeMaleMendelian Randomization AnalysisMiddle AgedUnited KingdomCalciumaction potentialcalciumcardiovascular diseaseselectrocardiographyelectrolyte

Identifiers

PMID33887147
PMCPMC8208093
OpenAlexW3156950955

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.