Integrative proteogenomic analyses discover novel plasma proteins that impact risk of ischemic stroke

Integrative proteogenomic analyses discover novel plasma proteins that impact risk of ischemic stroke | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Integrative proteogenomic analyses discover novel plasma proteins that impact risk of ischemic stroke Lazaros Belbasis, Adem von Ende, Parag Gajendragadkar, Elsa Valdes-Marquez, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7222618/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Understanding the proteins implicated in the pathogenesis of ischemic stroke is essential for developing novel prevention strategies. In this study, we compiled the largest available data sources for proteins and stroke to conduct Mendelian randomization (MR) using cis protein quantitative trait loci of over 3,500 proteins across two proteomic platforms and assess their causal relationship with ischemic stroke and its risk factors. We identified 21 potentially causal associations between proteins and ischemic stroke or its subtypes at 5% false discovery rate, with 16 supported by co-localisation. Four proteins (CEP85, KNG1, MMUT, SPATA20) represented novel findings not previously implicated in ischemic stroke through MR or genome-wide association studies. Integration of evidence from phenome-wide MR, animal models and tissue-specific gene expression highlighted agonists of MMUT, CEP85 and GRK5, and inhibitors of F11 and KNG1 as the most promising targets for prevention of ischemic stroke. Our study provides the most comprehensive data integration to date supporting the identification and causal relevance of plasma proteins for ischemic stroke. Health sciences/Diseases/Neurological disorders/Cerebrovascular disorders/Stroke Biological sciences/Drug discovery/Target identification co-localisation Mendelian randomisation ischemic stroke proteomics Full Text Supplementary Files SupplementaryFigures.docx Supplementary Figures SupplementaryTables.xlsx Supplementary Tables Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7222618","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":493863250,"identity":"d8c21adc-82b6-49ba-b498-a4415fe3c91a","order_by":0,"name":"Lazaros Belbasis","email":"data:image/png;base64,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","orcid":"","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":true,"prefix":"","firstName":"Lazaros","middleName":"","lastName":"Belbasis","suffix":""},{"id":493863251,"identity":"d700da5d-ecec-4a5c-a90b-588415644ccc","order_by":1,"name":"Adem von Ende","email":"","orcid":"","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":false,"prefix":"","firstName":"Adem","middleName":"","lastName":"von Ende","suffix":""},{"id":493863252,"identity":"e3024840-c02a-465c-89a1-2d38a9f15d28","order_by":2,"name":"Parag Gajendragadkar","email":"","orcid":"","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":false,"prefix":"","firstName":"Parag","middleName":"","lastName":"Gajendragadkar","suffix":""},{"id":493863253,"identity":"d6142406-1f01-4169-ae9a-c1b0ec1c9b17","order_by":3,"name":"Elsa Valdes-Marquez","email":"","orcid":"","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":false,"prefix":"","firstName":"Elsa","middleName":"","lastName":"Valdes-Marquez","suffix":""},{"id":493863254,"identity":"b7269d56-280d-4c0d-af57-8d186ab1c407","order_by":4,"name":"Federico Murgia","email":"","orcid":"https://orcid.org/0000-0002-3608-845X","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":false,"prefix":"","firstName":"Federico","middleName":"","lastName":"Murgia","suffix":""},{"id":493863255,"identity":"4d9a1414-87df-411e-a713-7243f3a06dfc","order_by":5,"name":"Cornelia van Duijn","email":"","orcid":"https://orcid.org/0000-0002-2374-9204","institution":"Nuffield Department of Population Health, University of Oxford, Oxford, U.K.","correspondingAuthor":false,"prefix":"","firstName":"Cornelia","middleName":"van","lastName":"Duijn","suffix":""},{"id":493863249,"identity":"1724620b-4027-4126-b731-756b5c17e93a","order_by":6,"name":"Jemma C. 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