Impact of Y loss in blood on male atherosclerosis and cardiovascular risk

Impact of Y loss in blood on male atherosclerosis and cardiovascular risk | 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 Biological Sciences - Article Impact of Y loss in blood on male atherosclerosis and cardiovascular risk Lars Forsberg, Josefin Bjurling, Andrei Malinovschi, Tomas Jernberg, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8902444/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Atherosclerotic cardiovascular disease shows a marked male predominance(1–3), yet the biological basis for this disparity remains unclear. Mosaic loss of chromosome Y (LOY) in blood – a common, acquired and age associated mutation(4,5)- has been linked to mortality and major causes of death, including myocardial infarction(6,7). Experimental studies indicate that LOY in leukocytes is causally related to mortality(8) and promotes pathology across organs by impairing immunosurveillance of senescent cells(9), providing a mechanistic explanation for systemic effects of leukocyte Y loss. Whether LOY in blood contributes to atherosclerosis, however, is unknown. Here we show that LOY in blood is associated with subclinical and clinical atherosclerotic disease by analyzing two large, population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) and the UK Biobank. SNP array–derived estimates of LOY mosaicism in blood leukocytes revealed dose-dependent associations with prevalence of coronary atherosclerosis, more extensive segment involvement, greater coronary stenosis and calcified plaques in SCAPIS. In UK Biobank, LOY was associated with greater carotid intima–media thickness, atherosclerosis, and myocardial infarction. Together, these findings point to a potential association between LOY in blood and a spectrum of atherosclerotic outcomes, offering one possible explanation for the higher cardiovascular risk observed in men. Biological sciences/Genetics/Medical genetics Biological sciences/Genetics/Genetic markers Biological sciences/Immunology/Immunogenetics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Bjurlingsupplement.pdf Supplementary Information Bjurling et al. Cite Share Download PDF Status: Posted 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. 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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-8902444","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":604127160,"identity":"c0926b45-366b-450f-ba17-fc4a5e00b3d2","order_by":0,"name":"Lars 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Mosaic loss of chromosome Y (LOY) in blood – a common, acquired and age associated mutation(4,5)- has been linked to mortality and major causes of death, including myocardial infarction(6,7). Experimental studies indicate that LOY in leukocytes is causally related to mortality(8) and promotes pathology across organs by impairing immunosurveillance of senescent cells(9), providing a mechanistic explanation for systemic effects of leukocyte Y loss. Whether LOY in blood contributes to atherosclerosis, however, is unknown. Here we show that LOY in blood is associated with subclinical and clinical atherosclerotic disease by analyzing two large, population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) and the UK Biobank. SNP array–derived estimates of LOY mosaicism in blood leukocytes revealed dose-dependent associations with prevalence of coronary atherosclerosis, more extensive segment involvement, greater coronary stenosis and calcified plaques in SCAPIS. 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