{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:37:02Z","timestamp":1791005822007,"version":"4.1.0"},"reference-count":44,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/14\/5\/30893"],"award-info":[{"award-number":["RG\/14\/5\/30893"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Observational studies suggest that variations in normal range thyroid function are associated with cardiovascular diseases. However, it remains to be determined whether these associations are causal or not.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To test whether genetically determined variation in normal range thyroid function is causally associated with the risk of stroke and coronary artery disease (CAD) and investigate via which pathways these relations may be mediated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design, Setting, and Participants<\/jats:title>\n                  <jats:p>Mendelian randomization analyses for stroke and CAD using genetic instruments associated with normal range thyrotropin (TSH) and free thyroxine levels or Hashimoto\u2019s thyroiditis and Graves\u2019 disease. The potential mediating role of known stroke and CAD risk factors was examined. Publicly available summary statistics data were used.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A 1 standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (odds ratio [OR],\u20050.95; 95% confidence interval [CI], 0.91-0.99; P\u2005=\u20050.008). Multivariable MR analyses indicated that this effect is mainly mediated via atrial fibrillation. MR analyses did not show a causal association between normal range thyroid function and CAD. Secondary analyses showed a causal relationship between Hashimoto\u2019s thyroiditis and a 7% increased risk of CAD (OR, 1.07; 95% CI, 1.01-1.13; P\u2005=\u20050.026), which was mainly mediated via body mass index.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke, and CAD. We identify variation in normal range thyroid function and Hashimoto\u2019s thyroiditis as risk factors for stroke and CAD, respectively.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa239","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T02:03:41Z","timestamp":1588817021000},"page":"2634-2641","source":"Crossref","is-referenced-by-count":51,"title":["Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-1609","authenticated-orcid":false,"given":"Eirini","family":"Marouli","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Kus","sequence":"additional","affiliation":[{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Del Greco M","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Peeters","sequence":"additional","affiliation":[{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Deloukas","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, UK"},{"name":"Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-7858","authenticated-orcid":false,"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"issue":"1","key":"2021122109212986500_CIT0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacc.2017.04.052","article-title":"Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015","volume":"70","author":"Roth","year":"2017","journal-title":"J Am Coll Cardiol."},{"issue":"3","key":"2021122109212986500_CIT0002","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1157\/13116658","article-title":"[Cardiovascular risk factors. 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