{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:18:10Z","timestamp":1791235090489,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of the IUCPQ"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy\/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38\u20130.51, P = 2.6e\u221228] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39\u20130.76, P = 4.2e\u221204) but not with bleeding (OR = 1.13, 95% CI = 0.93\u20131.36, P = 2.2e\u221201). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58\u20130.64, P = 4.1e\u221285) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69\u20130.86, P = 4.1e\u221206) but not with bleeding (OR = 1.01, 95% CI = 0.95\u20131.08, P = 7.5e\u221201). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeae043","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T08:50:58Z","timestamp":1716799858000},"source":"Crossref","is-referenced-by-count":2,"title":["Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant 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Epidemiology and Biostatistics, School of Public Health, Imperial College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Th\u00e9riault","sequence":"additional","affiliation":[{"name":"Centre de recherche de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec , Y-3106, Pavillon Marguerite D'Youville, 2725 chemin Ste-Foy, Quebec, QC , Canada , G1V 4G5"},{"name":"Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Universit\u00e9 Laval , Quebec, QC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7017-5848","authenticated-orcid":false,"given":"Marie-Claude","family":"Vohl","sequence":"additional","affiliation":[{"name":"School of Nutrition, Universit\u00e9 Laval , Quebec, QC , Canada"},{"name":"Centre Nutrition, Sant\u00e9 et soci\u00e9t\u00e9 (NUTRISS), Institut sur la nutrition et les aliments 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