{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:31:06Z","timestamp":1781641866428,"version":"3.54.5"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">High plasma prekallikrein was reported to be associated with increased risks of stroke, but the causality for these associations remains unclear. We aimed to investigate the associations of genetically predicted plasma prekallikrein concentrations with all\u2010cause stroke, ischemic stroke, 3 ischemic stroke subtypes, and intracerebral hemorrhage (ICH) using a 2\u2010sample Mendelian randomization approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Seven independent prekallikrein\u2010related single\u2010nucleotide polymorphisms were identified as genetic instruments for prekallikrein based on a genome\u2010wide association study with 1000 European individuals. The summary statistics for all\u2010cause stroke, ischemic stroke, and ischemic stroke subtypes were obtained from the Multiancestry Genome\u2010wide Association Study of Stroke Consortium with 40\u2009585 cases and 406\u2009111 controls of European ancestry. The summary statistics for ICH were obtained from the ISGC (International Stroke Genetics Consortium) with 1545 ICH cases and 1481 controls of European ancestry. In the main analysis, the inverse\u2010variance weighted method was applied to estimate the associations of plasma prekallikrein concentrations with all\u2010cause stroke, ischemic stroke, ischemic stroke subtypes, and ICH. Genetically predicted high plasma prekallikrein levels were significantly associated with elevated risks of all\u2010cause stroke (odds ratio [OR] per SD increase, 1.04 [95% CI, 1.02\u20131.06];\n              <jats:italic>P<\/jats:italic>\n              =5.44\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ), ischemic stroke (OR per SD increase, 1.05 [95% CI, 1.03\u20131.07];\n              <jats:italic>P<\/jats:italic>\n              =1.42\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ), cardioembolic stroke (OR per SD increase, 1.08 [95% CI, 1.03\u20131.12];\n              <jats:italic>P<\/jats:italic>\n              =3.75\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              ), and small vessel stroke (OR per SD increase, 1.11 [95% CI, 1.06\u20131.17];\n              <jats:italic>P<\/jats:italic>\n              =3.02\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ). However, no significant associations were observed for genetically predicted prekallikrein concentrations with large artery stroke and ICH.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">This Mendelian randomization study found that genetically predicted high plasma prekallikrein concentrations were associated with increased risks of all\u2010cause stroke, ischemic stroke, cardioembolic stroke, and small vessel stroke, indicating that prekallikrein might have a critical role in the development of stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.030525","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:35:57Z","timestamp":1691663757000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Association Between Prekallikrein and Stroke: A Mendelian Randomization Study"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2967-6058","authenticated-orcid":false,"given":"Yinan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and 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Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Suzhou Medical College of Soochow University Suzhou 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