{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T08:00:55Z","timestamp":1780992055514,"version":"3.54.1"},"reference-count":58,"publisher":"Royal College of Psychiatrists","issue":"3","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec id=\"S000712502400165X_sec_a1\"><jats:title>Background<\/jats:title><jats:p>An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502400165X_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>To assess shared genetic liability and potential causal effects between schizophrenia and arrhythmic disorders and electrocardiogram (ECG) traits.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502400165X_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53 386 cases, 77 258 controls), arrhythmic disorders (atrial fibrillation, 55 114 cases, 482 295 controls; Brugada syndrome, 2820 cases, 10 001 controls) and ECG traits (heart rate (variability), PR interval, QT interval, JT interval and QRS duration, <jats:italic>n<\/jats:italic> = 46 952\u2013293 051). We examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Bidirectional causal relations between schizophrenia and arrhythmic disorders and ECG traits were explored using Mendelian randomisation.<\/jats:p><\/jats:sec><jats:sec id=\"S000712502400165X_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>There was no evidence for global genetic correlation, except between schizophrenia and Brugada syndrome (<jats:italic>r<\/jats:italic><jats:sub>g<\/jats:sub> = 0.14, 95% CIs = 0.06\u20130.22, <jats:italic>P<\/jats:italic> = 4.0E\u221204). In contrast, strong positive and negative local correlations between schizophrenia and all cardiac traits were found across the genome. In the most strongly associated regions, genes related to immune and viral response mechanisms were overrepresented. Mendelian randomisation indicated that liability to schizophrenia causally increases Brugada syndrome risk (beta = 0.14, CIs = 0.03\u20130.25, <jats:italic>P<\/jats:italic> = 0.009) and heart rate during activity (beta = 0.25, CIs = 0.05\u20130.45, <jats:italic>P<\/jats:italic> = 0.015).<\/jats:p><\/jats:sec><jats:sec id=\"S000712502400165X_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Despite little evidence for global genetic correlation, specific genomic regions and biological pathways emerged that are important for both schizophrenia and arrhythmia. The putative causal effect of liability to schizophrenia on Brugada syndrome warrants increased cardiac monitoring and early medical intervention in people with schizophrenia.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.165","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T08:33:52Z","timestamp":1731054832000},"page":"153-161","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":5,"title":["Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: genetic exploration of population samples"],"prefix":"10.1192","volume":"226","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-3390","authenticated-orcid":false,"given":"Jorien L.","family":"Treur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs B.","family":"Thijssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J. 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Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0), which permits non-commercial re-use, distribution, and reproduction in any medium, provided that no alterations are made and the original article is properly cited. The written permission of Cambridge University Press must be obtained prior to any commercial use and\/or adaptation of the article.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}