{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:58:15Z","timestamp":1765961895948,"version":"3.48.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Life Science Research Partners"},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["22J30004"],"award-info":[{"award-number":["22J30004"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["512461526"],"award-info":[{"award-number":["512461526"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["302210\/Z\/23\/Z"],"award-info":[{"award-number":["302210\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["221680\/Z\/20\/Z"],"award-info":[{"award-number":["221680\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["#1350181"],"award-info":[{"award-number":["#1350181"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI170850"],"award-info":[{"award-number":["R01AI170850"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01Hl161365"],"award-info":[{"award-number":["R01Hl161365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/23\/121"],"award-info":[{"award-number":["C14\/23\/121"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G072921N"],"award-info":[{"award-number":["G072921N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1843423N"],"award-info":[{"award-number":["1843423N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021-03050"],"award-info":[{"award-number":["2021-03050"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2023.0141"],"award-info":[{"award-number":["2023.0141"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006350","name":"Stiftelsen Clas Groschinskys Minnesfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009745","name":"Emil och Wera Cornells Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010769","name":"Petrus och Augusta Hedlunds Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Philip-S\u00f6rensen foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cardiovasc Res"],"DOI":"10.1038\/s44161-025-00749-4","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T16:02:56Z","timestamp":1765900976000},"page":"1662-1676","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8146-9692","authenticated-orcid":false,"given":"Art","family":"Schuermans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-4713","authenticated-orcid":false,"given":"Andreas","family":"Verstraete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-5239","authenticated-orcid":false,"given":"Vilma","family":"Lammi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-5646","authenticated-orcid":false,"given":"Tomoko","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddalena","family":"Ardissino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5606-376X","authenticated-orcid":false,"given":"Jef","family":"Van den Eynde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6347-2281","authenticated-orcid":false,"given":"Benjamin B.","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-3659","authenticated-orcid":false,"given":"Marios K.","family":"Georgakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Guillen-Guio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise V.","family":"Wain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"PHOSP-COVID Collaborative Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-8426","authenticated-orcid":false,"given":"Johan","family":"Van Weyenbergh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam J.","family":"Lewandowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betty","family":"Raman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-1249","authenticated-orcid":false,"given":"Hugo","family":"Zeberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-6429","authenticated-orcid":false,"given":"Hanna M.","family":"Ollila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-8760","authenticated-orcid":false,"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8402-7435","authenticated-orcid":false,"given":"Pradeep","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5021","authenticated-orcid":false,"given":"Michael C.","family":"Honigberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4381-2442","authenticated-orcid":false,"given":"Kathleen","family":"Freson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Vanassche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8698-2858","authenticated-orcid":false,"given":"Peter","family":"Verhamme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"749_CR1","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1001\/jama.2022.18931","volume":"328","author":"T Vos","year":"2022","unstructured":"Vos, T. et al. Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA 328, 1604\u20131615 (2022).","journal-title":"JAMA"},{"key":"749_CR2","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","volume":"22","author":"JB Soriano","year":"2022","unstructured":"Soriano, J. B., Murthy, S., Marshall, J. C., Relan, P. & Diaz, J. V. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect. Dis. 22, e102\u2013e107 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"749_CR3","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","volume":"21","author":"HE Davis","year":"2023","unstructured":"Davis, H. E., McCorkell, L., Vogel, J. M. & Topol, E. J. Long COVID: major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 133\u2013146 (2023).","journal-title":"Nat. Rev. Microbiol."},{"key":"749_CR4","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1093\/cid\/ciab611","volume":"74","author":"J Seeble","year":"2022","unstructured":"Seeble, J. et al. Persistent symptoms in adult patients 1 year after coronavirus disease 2019 (COVID-19): a prospective cohort study. Clin. Infect. Dis. 74, 1191\u20131198 (2022).","journal-title":"Clin. Infect. Dis."},{"key":"749_CR5","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1038\/s41467-022-29513-z","volume":"13","author":"VT Tran","year":"2022","unstructured":"Tran, V. T., Porcher, R., Pane, I. & Ravaud, P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat. Commun. 13, 1812 (2022).","journal-title":"Nat. Commun."},{"key":"749_CR6","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/s42003-023-04805-2","volume":"6","author":"X Huang","year":"2023","unstructured":"Huang, X. et al. Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism. Commun. Biol. 6, 441 (2023).","journal-title":"Commun. Biol."},{"key":"749_CR7","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1038\/s41591-023-02525-y","volume":"29","author":"M Taquet","year":"2023","unstructured":"Taquet, M. et al. Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization. Nat. Med. 29, 2498\u20132508 (2023).","journal-title":"Nat. Med."},{"key":"749_CR8","doi-asserted-by":"publisher","first-page":"eadg7942","DOI":"10.1126\/science.adg7942","volume":"383","author":"C Cervia-Hasler","year":"2024","unstructured":"Cervia-Hasler, C. et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science 383, eadg7942 (2024).","journal-title":"Science"},{"key":"749_CR9","doi-asserted-by":"crossref","unstructured":"Davies, M. Long covid patients travel abroad for expensive and experimental \u2018blood washing\u2019. BMJ 378, o1671 (2022).","DOI":"10.1136\/bmj.o1671"},{"key":"749_CR10","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s43586-021-00056-9","volume":"1","author":"E Uffelmann","year":"2021","unstructured":"Uffelmann, E. et al. Genome-wide association studies. Nat. Rev. Methods Primers 1, 59 (2021).","journal-title":"Nat. Rev. Methods Primers"},{"key":"749_CR11","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","volume":"362","author":"NM Davies","year":"2018","unstructured":"Davies, N. M., Holmes, M. V. & Davey Smith, G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ 362, k601 (2018).","journal-title":"BMJ"},{"key":"749_CR12","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","volume":"2","author":"E Sanderson","year":"2022","unstructured":"Sanderson, E. et al. Mendelian randomization. Nat. Rev. Methods Primers 2, 6 (2022).","journal-title":"Nat. Rev. Methods Primers"},{"key":"749_CR13","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","volume":"37","author":"S Burgess","year":"2013","unstructured":"Burgess, S., Butterworth, A. & Thompson, S. G. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet. Epidemiol. 37, 658\u2013665 (2013).","journal-title":"Genet. Epidemiol."},{"key":"749_CR14","doi-asserted-by":"crossref","unstructured":"Ardissino, M. et al. Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association. Eur. Heart J. 45, 443\u2212454 (2023).","DOI":"10.1093\/eurheartj\/ehad631"},{"key":"749_CR15","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41591-021-01310-z","volume":"27","author":"L Gaziano","year":"2021","unstructured":"Gaziano, L. et al. Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19. Nat. Med. 27, 668\u2013676 (2021).","journal-title":"Nat. Med."},{"key":"749_CR16","doi-asserted-by":"publisher","first-page":"e658","DOI":"10.1016\/S2665-9913(20)30345-3","volume":"2","author":"J Bovijn","year":"2020","unstructured":"Bovijn, J., Lindgren, C. M. & Holmes, M. V. Genetic variants mimicking therapeutic inhibition of IL-6 receptor signaling and risk of COVID-19. Lancet Rheumatol. 2, e658\u2013e659 (2020).","journal-title":"Lancet Rheumatol."},{"key":"749_CR17","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/s41586-021-03767-x","volume":"600","author":"MEK Niemi","year":"2021","unstructured":"Niemi, M. E. K. et al. Mapping the human genetic architecture of COVID-19. Nature 600, 472\u2013477 (2021).","journal-title":"Nature"},{"key":"749_CR18","doi-asserted-by":"crossref","unstructured":"REMAP-CAP Investigators et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N. Engl. J. Med. 384, 1491\u20131502 (2021).","DOI":"10.1056\/NEJMoa2100433"},{"key":"749_CR19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1001\/jama.2021.11330","volume":"326","author":"WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al.","year":"2021","unstructured":"WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA 326, 499\u2013518 (2021).","journal-title":"JAMA"},{"key":"749_CR20","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41586-023-06388-8","volume":"620","author":"K Trajanoska","year":"2023","unstructured":"Trajanoska, K. et al. From target discovery to clinical drug development with human genetics. Nature 620, 737\u2013745 (2023).","journal-title":"Nature"},{"key":"749_CR21","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/aje\/kwt084","volume":"178","author":"BL Pierce","year":"2013","unstructured":"Pierce, B. L. & Burgess, S. Efficient design for mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am. J. Epidemiol. 178, 1177\u20131184 (2013).","journal-title":"Am. J. Epidemiol."},{"key":"749_CR22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","volume":"613","author":"MI Kurki","year":"2023","unstructured":"Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508\u2013518 (2023).","journal-title":"Nature"},{"key":"749_CR23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s42003-024-05872-9","volume":"7","author":"JT Leinonen","year":"2024","unstructured":"Leinonen, J. T., Pirinen, M. & Tukiainen, T. Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother\u2013child pairs. Commun. Biol. 7, 175 (2024).","journal-title":"Commun. Biol."},{"key":"749_CR24","unstructured":"Access results. FinnGen. https:\/\/www.finngen.fi\/en\/access_results."},{"key":"749_CR25","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1038\/s41588-025-02100-w","volume":"57","author":"V Lammi","year":"2025","unstructured":"Lammi, V. et al. Genome-wide association study of long COVID. Nat Genet. 57, 1402\u20131417 (2025).","journal-title":"Nat Genet."},{"key":"749_CR26","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess, S. & Thompson, S. G. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur. J. Epidemiol. 32, 377 (2017).","journal-title":"Eur. J. Epidemiol."},{"key":"749_CR27","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","volume":"13","author":"G Hemani","year":"2017","unstructured":"Hemani, G., Tilling, K. & Davey Smith, G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet. 13, e1007081 (2017).","journal-title":"PLoS Genet."},{"key":"749_CR28","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1038\/s41588-019-0519-3","volume":"51","author":"D Klarin","year":"2019","unstructured":"Klarin, D. et al. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease. Nat. Genet. 51, 1574\u20131579 (2019).","journal-title":"Nat. Genet."},{"key":"749_CR29","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/S2213-2600(21)00383-0","volume":"9","author":"RA Evans","year":"2021","unstructured":"Evans, R. A. et al. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir. Med. 9, 1275\u20131287 (2021).","journal-title":"Lancet Respir. Med."},{"key":"749_CR30","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1093\/ije\/dyad165","volume":"53","author":"O Elneima","year":"2024","unstructured":"Elneima, O. et al. Cohort profile: post-hospitalisation COVID-19 (PHOSP-COVID) study. Int. J. Epidemiol. 53, 165 (2024).","journal-title":"Int. J. Epidemiol."},{"key":"749_CR31","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1001\/jama.2020.13372","volume":"324","author":"S Bilaloglu","year":"2020","unstructured":"Bilaloglu, S. et al. Thrombosis in hospitalized patients with COVID-19 in a New York City health system. JAMA 324, 799\u2013801 (2020).","journal-title":"JAMA"},{"key":"749_CR32","doi-asserted-by":"publisher","first-page":"e069590","DOI":"10.1136\/bmj-2021-069590","volume":"377","author":"I Katsoularis","year":"2022","unstructured":"Katsoularis, I. et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ 377, e069590 (2022).","journal-title":"BMJ"},{"key":"749_CR33","doi-asserted-by":"publisher","first-page":"E7","DOI":"10.1038\/s41586-023-06355-3","volume":"621","author":"M Kanai","year":"2023","unstructured":"Kanai, M. et al. A second update on mapping the human genetic architecture of COVID-19. Nature 621, E7\u2013E26 (2023).","journal-title":"Nature"},{"key":"749_CR34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1093\/eurheartj\/ehp504","volume":"31","author":"DJ Angiolillo","year":"2010","unstructured":"Angiolillo, D. J., Capodanno, D. & Goto, S. Platelet thrombin receptor antagonism and atherothrombosis. Eur. Heart J. 31, 17\u201328 (2010).","journal-title":"Eur. Heart J."},{"key":"749_CR35","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1080\/00207230500120294","volume":"16","author":"SMG Smith","year":"2005","unstructured":"Smith, S. M. G. et al. PAR-1 genotype influences platelet aggregation and procoagulant responses in patients with coronary artery disease prior to and during clopidogrel therapy. Platelets 16, 340\u2013345 (2005).","journal-title":"Platelets"},{"key":"749_CR36","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1182\/blood-2002-07-2149","volume":"101","author":"A Dupont","year":"2003","unstructured":"Dupont, A. et al. An intronic polymorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN. Blood 101, 1833\u20131840 (2003).","journal-title":"Blood"},{"key":"749_CR37","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun, B. B. et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622, 329\u2013338 (2023).","journal-title":"Nature"},{"key":"749_CR38","doi-asserted-by":"crossref","unstructured":"Woolf, B. et al. A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study. BMJ 383, e076197 (2023).","DOI":"10.1136\/bmj-2023-076197"},{"key":"749_CR39","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.ajhg.2022.04.001","volume":"109","author":"V Zuber","year":"2022","unstructured":"Zuber, V. et al. Combining evidence from Mendelian randomization and colocalization: review and comparison of approaches. Am. J. Hum. Genet. 109, 767\u2013782 (2022).","journal-title":"Am. J. Hum. Genet."},{"key":"749_CR40","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","volume":"550","author":"F Aguet","year":"2017","unstructured":"Aguet, F. et al. Genetic effects on gene expression across human tissues. Nature 550, 204\u2013213 (2017).","journal-title":"Nature"},{"key":"749_CR41","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1182\/blood.2020006115","volume":"137","author":"K Kammers","year":"2021","unstructured":"Kammers, K. et al. Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole-genome and RNA sequencing. Blood 137, 959\u2013968 (2021).","journal-title":"Blood"},{"key":"749_CR42","doi-asserted-by":"publisher","first-page":"23290","DOI":"10.1074\/jbc.273.36.23290","volume":"273","author":"ML Kahn","year":"1998","unstructured":"Kahn, M. L., Hammes, S. R., Botka, C. & Coughlin, S. R. Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J. Biol. Chem. 273, 23290\u201323296 (1998).","journal-title":"J. Biol. Chem."},{"key":"749_CR43","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12933-021-01359-7","volume":"20","author":"E Pretorius","year":"2021","unstructured":"Pretorius, E. et al. Persistent clotting protein pathology in Long COVID\/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc. Diabetol. 20, 172 (2021).","journal-title":"Cardiovasc. Diabetol."},{"key":"749_CR44","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41586-022-05165-3","volume":"611","author":"A Mishra","year":"2022","unstructured":"Mishra, A. et al. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 611, 115\u2013123 (2022).","journal-title":"Nature"},{"key":"749_CR45","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1038\/s41591-022-01891-3","volume":"28","author":"C Tcheandjieu","year":"2022","unstructured":"Tcheandjieu, C. et al. Large-scale genome-wide association study of coronary artery disease in genetically diverse populations. Nat. Med. 28, 1679\u20131692 (2022).","journal-title":"Nat. Med."},{"key":"749_CR46","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1161\/CIRCULATIONAHA.121.057394","volume":"145","author":"H Stevens","year":"2022","unstructured":"Stevens, H., Canovas, R., Tran, H., Peter, K. & McFadyen, J. D. Inherited thrombophilias are associated with a higher risk of COVID-19\u2013associated venous thromboembolism: a prospective population-based cohort study. Circulation 145, 940\u2013942 (2022).","journal-title":"Circulation"},{"key":"749_CR47","doi-asserted-by":"crossref","unstructured":"ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N. Engl. J. Med. 385, 790\u2013802 (2021).","DOI":"10.1056\/NEJMoa2105911"},{"key":"749_CR48","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1001\/jamainternmed.2021.6203","volume":"181","author":"AC Spyropoulos","year":"2021","unstructured":"Spyropoulos, A. C. et al. Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern. Med. 181, 1612\u20131620 (2021).","journal-title":"JAMA Intern. Med."},{"key":"749_CR49","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/s41586-024-07873-4","volume":"633","author":"JK Ryu","year":"2024","unstructured":"Ryu, J. K. et al. Fibrin drives thromboinflammation and neuropathology in COVID-19. Nature 633, 905\u2013913 (2024).","journal-title":"Nature"},{"key":"749_CR50","doi-asserted-by":"publisher","first-page":"e487","DOI":"10.1093\/cid\/ciac722","volume":"76","author":"Z Swank","year":"2023","unstructured":"Swank, Z. et al. Persistent circulating severe acute respiratory syndrome coronavirus 2 spike is associated with post-acute coronavirus disease 2019 sequelae. Clin. Infect. Dis. 76, e487\u2013e490 (2023).","journal-title":"Clin. Infect. Dis."},{"key":"749_CR51","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/35025229","volume":"407","author":"SR Coughlin","year":"2000","unstructured":"Coughlin, S. R. Thrombin signalling and protease-activated receptors. Nature 407, 258\u2013264 (2000).","journal-title":"Nature"},{"key":"749_CR52","doi-asserted-by":"publisher","first-page":"18592","DOI":"10.1074\/jbc.M310836200","volume":"279","author":"MJ Ludeman","year":"2004","unstructured":"Ludeman, M. J., Zheng, Y. W., Ishii, K. & Coughlin, S. R. Regulated shedding of PAR1 N-terminal exodomain from endothelial cells. J. Biol. Chem. 279, 18592\u201318599 (2004).","journal-title":"J. Biol. Chem."},{"key":"749_CR53","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1126\/science.1071699","volume":"296","author":"M Riewald","year":"2002","unstructured":"Riewald, M., Petrovan, R. J., Donner, A., Mueller, B. M. & Ruf, W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296, 1880\u20131882 (2002).","journal-title":"Science"},{"key":"749_CR54","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1111\/jth.12539","volume":"12","author":"YM Patel","year":"2014","unstructured":"Patel, Y. M. et al. A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding. J. Thromb. Haemost. 12, 716\u2013725 (2014).","journal-title":"J. Thromb. Haemost."},{"key":"749_CR55","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nature06663","volume":"452","author":"F Niessen","year":"2008","unstructured":"Niessen, F. et al. Dendritic cell PAR1\u2013S1P3 signalling couples coagulation and inflammation. Nature 452, 654\u2013658 (2008).","journal-title":"Nature"},{"key":"749_CR56","doi-asserted-by":"publisher","first-page":"2760","DOI":"10.1182\/bloodadvances.2021004360","volume":"5","author":"S Subramaniam","year":"2021","unstructured":"Subramaniam, S. et al. A thrombin-PAR1\/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C). Blood Adv. 5, 2760\u20132774 (2021).","journal-title":"Blood Adv."},{"key":"749_CR57","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1056\/NEJMoa1200933","volume":"366","author":"DA Morrow","year":"2012","unstructured":"Morrow, D. A. et al. Vorapaxar in the secondary prevention of atherothrombotic events. N. Engl. J. Med. 366, 1404\u20131413 (2012).","journal-title":"N. Engl. J. Med."},{"key":"749_CR58","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1056\/NEJMoa1109719","volume":"366","author":"P Tricoci","year":"2012","unstructured":"Tricoci, P. et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N. Engl. J. Med. 366, 20\u201333 (2012).","journal-title":"N. Engl. J. Med."},{"key":"749_CR59","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s11606-022-07997-1","volume":"38","author":"D Khullar","year":"2023","unstructured":"Khullar, D. et al. Racial\/ethnic disparities in post-acute sequelae of SARS-CoV-2 infection in New York: an EHR-based cohort study from the RECOVER program. J. Gen. Intern. Med. 38, 1127\u20131136 (2023).","journal-title":"J. Gen. Intern. Med."},{"key":"749_CR60","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/gepi.21998","volume":"40","author":"S Burgess","year":"2016","unstructured":"Burgess, S., Davies, N. M. & Thompson, S. G. Bias due to participant overlap in two-sample Mendelian randomization. Genet. Epidemiol. 40, 597\u2013608 (2016).","journal-title":"Genet. Epidemiol."},{"key":"749_CR61","unstructured":"FinnGen Public Documentation. https:\/\/finngen.gitbook.io\/documentation\/r10."},{"key":"749_CR62","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"The 1000 Genomes Project Consortium.","year":"2015","unstructured":"The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68\u201374 (2015).","journal-title":"Nature"},{"key":"749_CR63","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"749_CR64","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1214\/aoms\/1177731868","volume":"11","author":"A Wald","year":"1940","unstructured":"Wald, A. The fitting of straight lines if both variables are subject to error. Ann. Math. Stat. 11, 284\u2013300 (1940).","journal-title":"Ann. Math. Stat."},{"key":"749_CR65","doi-asserted-by":"crossref","unstructured":"Hemani, G. et al. The MR-base platform supports systematic causal inference across the human phenome. eLife 7, e34408 (2018).","DOI":"10.7554\/eLife.34408"},{"key":"749_CR66","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ije\/dyx034","volume":"46","author":"OO Yavorska","year":"2017","unstructured":"Yavorska, O. O. & Burgess, S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int. J. Epidemiol. 46, 1734\u20131739 (2017).","journal-title":"Int. J. Epidemiol."},{"key":"749_CR67","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden, J., Davey Smith, G., Haycock, P. C. & Burgess, S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40, 304\u2013314 (2016).","journal-title":"Genet. Epidemiol."},{"key":"749_CR68","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/ije\/dyx102","volume":"46","author":"FP Hartwig","year":"2017","unstructured":"Hartwig, F. P., Smith, G. D. & Bowden, J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int. J. Epidemiol. 46, 1985\u20131998 (2017).","journal-title":"Int. J. Epidemiol."},{"key":"749_CR69","doi-asserted-by":"crossref","unstructured":"Schuermans, A. et al. Genetic associations of circulating cardiovascular proteins with gestational hypertension and preeclampsia. JAMA Cardiol.9, 209\u2212220 (2024).","DOI":"10.1001\/jamacardio.2023.4994"},{"key":"749_CR70","doi-asserted-by":"crossref","unstructured":"Schuermans, A. et al. Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction. Nat. Cardiovasc. Res.3,1516\u22121530 (2024).","DOI":"10.1038\/s44161-024-00567-0"},{"key":"749_CR71","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1161\/CIRCULATIONAHA.121.056663","volume":"145","author":"A Henry","year":"2022","unstructured":"Henry, A. et al. Therapeutic targets for heart failure identified using proteomics and Mendelian randomization. Circulation 145, 1205\u20131217 (2022).","journal-title":"Circulation"},{"key":"749_CR72","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41467-022-28119-9","volume":"13","author":"O Mahmoud","year":"2022","unstructured":"Mahmoud, O., Dudbridge, F., Davey Smith, G., Munafo, M. & Tilling, K. A robust method for collider bias correction in conditional genome-wide association studies. Nat. Commun. 13, 619 (2022).","journal-title":"Nat. Commun."},{"key":"749_CR73","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jclinepi.2015.09.016","volume":"70","author":"JM Gaziano","year":"2016","unstructured":"Gaziano, J. M. et al. Million Veteran Program: a mega-biobank to study genetic influences on health and disease. J. Clin. Epidemiol. 70, 214\u2013223 (2016).","journal-title":"J. Clin. Epidemiol."},{"key":"749_CR74","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"749_CR75","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203\u2013209 (2018).","journal-title":"Nature"},{"key":"749_CR76","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei, C. et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 10, e1004383 (2014).","journal-title":"PLoS Genet."},{"key":"749_CR77","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","volume":"369","author":"F Aguet","year":"2020","unstructured":"Aguet, F. et al. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318\u20131330 (2020).","journal-title":"Science"},{"key":"749_CR78","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1001\/jama.295.12.1420","volume":"295","author":"DM Becker","year":"2006","unstructured":"Becker, D. M. et al. Sex differences in platelet reactivity and response to low-dose aspirin therapy. JAMA 295, 1420\u20131427 (2006).","journal-title":"JAMA"},{"key":"749_CR79","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","volume":"590","author":"D Taliun","year":"2021","unstructured":"Taliun, D. et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590, 290\u2013299 (2021).","journal-title":"Nature"}],"container-title":["Nature Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44161-025-00749-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-025-00749-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44161-025-00749-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:02:20Z","timestamp":1765958540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44161-025-00749-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":79,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["749"],"URL":"https:\/\/doi.org\/10.1038\/s44161-025-00749-4","relation":{},"ISSN":["2731-0590"],"issn-type":[{"type":"electronic","value":"2731-0590"}],"subject":[],"published":{"date-parts":[[2025,12,16]]},"assertion":[{"value":"7 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.S. is a full-time employee of Bristol Myers Squibb. M.K.G. has consulted for Tourmaline Bio and serves on the Editorial Board of Neurology, both not relevant to this work. L.V.W. reports research funding from GlaxoSmithKline, Genentech and Orion Pharma and consultancy for Galapagos and GlaxoSmithKline, outside of the submitted work. C.E.B. has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. M.C.H. reports research funding from Genentech, site principal investigator work for Novartis, consulting fees from Comanche Biopharma and advisory board service for Miga Health, all unrelated to the present work. K.F. received research grants from Novo Nordisk and Swedish Orphan Biovitrum AB (Sobi). T.V. has participated in advisory boards and\/or acted as a speaker on behalf of Bayer, Bristol Myers Squibb\/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Leo Pharma and Sanofi Aventis. P.V. has received research funding from Bayer, Bristol Myers Squibb, Pfizer and Leo Pharma and honoraria from Bayer, Pfizer, Bristol Myers Squibb, Daiichi-Sankyo, Sanofi-Aventis, Leo Pharma, Anthos Therapeutics and AstraZeneca. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}