{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:57:16Z","timestamp":1791619036251,"version":"4.3.4"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>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).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Independent lead variants from a newly performed genome-wide association study for serum calcium in &gt;300\u2009000 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\u2009226 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.003231","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T21:02:10Z","timestamp":1619125330000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Genetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9831-6817","authenticated-orcid":true,"given":"William J.","family":"Young","sequence":"first","affiliation":[{"name":"Clinical 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."},{"name":"Barts Heart Centre, St Bartholomew\u2019s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-1386","authenticated-orcid":true,"given":"Helen R.","family":"Warren","sequence":"additional","affiliation":[{"name":"Clinical 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."},{"name":"NIHR Barts Cardiovascular Biomedical Research Unit (H.R.W., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis O.","family":"Mook-Kanamori","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology (D.O.M.-K.), Leiden University Medical Center, the Netherlands."},{"name":"Department of Public Health and Primary Care (D.O.M.-K.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-5866","authenticated-orcid":true,"given":"Julia","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Clinical 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."},{"name":"Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8897-558X","authenticated-orcid":true,"given":"Stefan","family":"van Duijvenboden","sequence":"additional","affiliation":[{"name":"Clinical 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."},{"name":"Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5773-0344","authenticated-orcid":true,"given":"Michele","family":"Orini","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, St Bartholomew\u2019s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)."},{"name":"Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-4151","authenticated-orcid":true,"given":"Andrew","family":"Tinker","sequence":"additional","affiliation":[{"name":"Clinical 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."},{"name":"NIHR Barts Cardiovascular Biomedical Research Unit (H.R.W., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (D.v.H., R.N.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9055-9267","authenticated-orcid":true,"given":"Pier D.","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, St Bartholomew\u2019s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)."},{"name":"Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-8359","authenticated-orcid":true,"given":"J. 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