{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:30:53Z","timestamp":1776954653599,"version":"3.51.4"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>Drug-induced long QT syndrome (diLQTS) is an adverse reaction from over 150 FDA-approved medications, posing the risk of triggering <jats:italic toggle=\"yes\">torsades de pointes<\/jats:italic> and sudden death. While common genetic variants may modestly impact QT interval individually, their collective effect can significantly amplify risk of diLQTS. Consequently, this study aimed to validate a polygenic risk score (PRS) for diLQTS previously proposed by Strauss <jats:italic toggle=\"yes\">et al<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A retrospective cohort study was conducted utilizing patients from the Michigan Genomics Initiative prescribed 27 high-risk QT-prolonging drugs and an ECG during the prescription. The primary outcome was marked prolongation of the QTc interval (either &gt;60\u2005ms change from baseline or &gt;500\u2005ms absolute value) during treatment with a high-risk QT-prolonging drug.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The primary outcome occurred in 12.0% of <jats:italic toggle=\"yes\">n<\/jats:italic>\u2005=\u20056070 self-reported White, 12.4% of 558 African American, and 8.2% of 110 Asian patients. The PRS significantly associated with diLQTS in White patients [adjusted odds ratio\u2005=\u20051.44 (95% CI: 1.09\u20131.89); <jats:italic toggle=\"yes\">P<\/jats:italic>\u2005=\u20050.009]. However the study lacked sufficient statistical power to confirm the PRS as a risk factor in African Americans [adjusted odds ratio\u2005=\u20052.18 (95% CI: 0.98\u20135.49); <jats:italic toggle=\"yes\">P<\/jats:italic>\u2005=\u20050.073] and Asians [adjusted odds ratio\u2005=\u20053.21 (95% CI: 0.69\u201316.87); <jats:italic toggle=\"yes\">P<\/jats:italic>\u2005=\u20050.139] due to smaller sample sizes in these groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The previously published PRS for diLQTS was validated in a large, real-world cohort, demonstrating its potential as a tool for identifying high-risk patients. Incorporating this PRS into routine clinical practice could enable proactive measures to prevent life-threatening diLQTS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000548","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T14:00:53Z","timestamp":1730210453000},"page":"45-56","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort"],"prefix":"10.1097","volume":"35","author":[{"given":"Ana I.","family":"Lopez-Medina","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra M.","family":"Campos-Staffico","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choudhary Anwar A.","family":"Chahal","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, Pennsylvania"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Cardiology, Barts Heart Centre"},{"name":"William Harvey Research Institute, Queen Mary University of London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliet P.","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Volkers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omer","family":"Berenfeld","sequence":"additional","affiliation":[{"name":"Center for Arrhythmia Research, Departments of Internal Medicine \u2013 Cardiology, Biomedical Engineering, and Applied Physics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine A.","family":"Luzum","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"R1-20241107","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1161\/01.CIR.30.1.17","article-title":"Quinidine syncope. 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