{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:06:07Z","timestamp":1792757167787,"version":"4.5.0"},"reference-count":51,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2021,9]]},"abstract":"\n Background:<\/jats:title>\n Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on hemostasis, coagulation, and fibrinolysis are unknown.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n In a two-sample Mendelian randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism (\n N<\/jats:italic>\n \u2009=\u2009134,641), normal-range thyrotropin (TSH;\n N<\/jats:italic>\n \u2009=\u200954,288) and free thyroxine (fT4) (\n N<\/jats:italic>\n \u2009=\u200949,269), hyperthyroidism (\n N<\/jats:italic>\n \u2009=\u200951,823), and thyroid peroxidase antibody positivity (\n N<\/jats:italic>\n \u2009=\u200925,821) on coagulation (activated partial thromboplastin time, von Willebrand factor [VWF], factor VIII [FVIII], prothrombin time, factor VII, fibrinogen) and fibrinolysis (D-dimer, tissue plasminogen activator [TPA], plasminogen activator inhibitor-1) from the CHARGE Hemostasis Consortium (\n N<\/jats:italic>\n \u2009=\u20092583\u2013120,246). Inverse-variance-weighted random effects were the main MR analysis followed by sensitivity analyses. Two-sided\n p<\/jats:italic>\n \u2009<\u20090.05 was nominally significant, and\n p<\/jats:italic>\n \u2009<\u20090.0011[\u2009=\u20090.05\/(5 exposures\u2009\u00d7\u20099 outcomes)] was Bonferroni significant for the main MR analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Genetically increased TSH was associated with decreased VWF [\u03b2(SE)\u2009=\u2009\u22120.020(0.006),\n p<\/jats:italic>\n \u2009=\u20090.001] and with decreased fibrinogen [\u03b2(SE)\u2009=\u2009\u22120.008(0.002),\n p<\/jats:italic>\n \u2009=\u20090.001]. Genetically increased fT4 was associated with increased VWF [\u03b2(SE)\u2009=\u20090.028(0.011),\n p<\/jats:italic>\n \u2009=\u20090.012]. Genetically predicted hyperthyroidism was associated with increased VWF [\u03b2(SE)\u2009=\u20090.012(0.004),\n p<\/jats:italic>\n \u2009=\u20090.006] and increased FVIII [\u03b2(SE)\u2009=\u20090.013(0.005),\n p<\/jats:italic>\n \u2009=\u20090.007]. Genetically predicted hypothyroidism and hyperthyroidism were associated with decreased TPA [\u03b2(SE)\u2009=\u2009\u22120.009(0.024),\n p<\/jats:italic>\n \u2009=\u20090.024] and increased TPA [\u03b2(SE)\u2009=\u20090.022(0.008),\n p<\/jats:italic>\n \u2009=\u20090.008], respectively. MR sensitivity analyses showed similar direction but lower precision. Other coagulation and fibrinolytic factors were inconclusive.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n In the largest genetic studies currently available, genetically increased TSH and fT4 may be associated with decreased and increased synthesis of VWF, respectively. Since Bonferroni correction may be too conservative given the correlation between the analyzed traits, we cannot reject nominal associations of thyroid traits with coagulation or fibrinolytic factors.<\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/thy.2021.0055","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:38:06Z","timestamp":1625186286000},"page":"1305-1315","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Effects of Thyroid Function on Hemostasis, Coagulation, and Fibrinolysis: A Mendelian Randomization Study"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-4375","authenticated-orcid":false,"given":"Christina","family":"Ellervik","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, USA."},{"name":"Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."},{"name":"Department of Data and Data Support, Region Zealand, Sor\u00f8, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Mora","sequence":"additional","affiliation":[{"name":"Center for Lipid Metabolomics, Division of Preventive Medicine; Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-6900","authenticated-orcid":false,"given":"Aleksander","family":"Ku\u015b","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases; 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-2101","authenticated-orcid":false,"given":"Bj\u00f8rn","family":"\u00c5svold","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway."},{"name":"Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Marouli","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."}],"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, United Kingdom."},{"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"}]},{"given":"Rosalie B.T.M.","family":"Sterenborg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases; Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 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, Greifswald, Germany."},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom."},{"name":"Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sabater-Lleal","sequence":"additional","affiliation":[{"name":"Genomics of Complex Diseases Group, Research Institute Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain."},{"name":"Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Huffman","sequence":"additional","affiliation":[{"name":"Scientific Director for Genomics Research, Center for Population Genomics, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute's The Framingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David-Alexandre","family":"Tr\u00e9gouet","sequence":"additional","affiliation":[{"name":"INSERM U1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, Washington, USA."},{"name":"Kaiser Permamente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, Washington, USA."},{"name":"Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases; 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Chan School of Public Health, Boston, Massachusetts, USA."},{"name":"Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA."},{"name":"Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-1324","authenticated-orcid":false,"given":"Alisa D.","family":"Kjaergaard","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-769018"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01642.x"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12275"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1999.00719.x"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0801"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2644"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-1249"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12573"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-07-0496"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04430.x"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04818.x"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-253724"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0576"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13970"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034442"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06356-1"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3570"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003266"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6681"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4352"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004123"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.4635"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002468"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0167"},{"key":"e_1_3_5_26_2","author":"Marouli E","unstructured":"Marouli E, , Kus A, , Del Greco MF, , Chaker L, , Peeters R, , Teumer A, , Deloukas P, Medici M 2020 Thyroid function affects the risk of stroke via atrial fibrillation: a Mendelian randomization study. 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