Mendelian randomization and single-cell analysis reveal relationships between sleep disorders and myocardial infarction

Mendelian randomization and single-cell analysis reveal relationships between sleep disorders and myocardial infarction | 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 Mendelian randomization and single-cell analysis reveal relationships between sleep disorders and myocardial infarction Zhihuan Luo, Pan Song, Bangji Xiong, Kun Hao, Yongpan Liu, Jinlong Jiang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4291368/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background Myocardial infarction (MI) and sleep apnoea are common diseases, and epidemiologic evidence suggests that the two are related. Methods Our research relied on genome-wide association summary statistics (GWAS) pertaining to patients diagnosed with sleep apnoea, snoring, insomnia, or narcolepsy, as well as individuals diagnosed with MI. Using a bidirectional Mendelian randomization (MR) approach, we investigated the relationships between MI and sleep apnoea, snoring, insomnia and narcolepsy. In addition, colocalization analysis was used to identify genes whose increased expression may contribute to sleep disorders. Subsequently, we illustrated that the upregulation of these genes serves as a negative prognostic factor for MI through the application of summary-data-based MR (SMR). Furthermore, we analysedsingle-cell data obtained from individuals with MI to elucidate the subcellular localization of these genes and assess the enriched pathways. Results Bidirectional MR analysis suggested no causal association between sleep apnoea and MI. Snoring, insomnia, and narcolepsy are risk factors for MI. The genes associated with snoring, insomnia, and narcolepsy were all colocalized with eQTLs. SMR demonstrated that these genes are risk factors for MI. Single-cell analysis revealed that these genes were predominantly localized to cardiac endothelial cells and enriched in the Rap1 pathway. Conclusion Our study revealedthat snoring, insomnia, and narcolepsy are risk factors for MI. The primary mechanism could involve sleep disorders inducing alterations in the expression abundance of LINC02210, LRRC37A, LRRC37A2, KANSL1-AS1, and DND1P1, thereby increasing the risk of MI via the Rap1 pathway. Health sciences/Cardiology/Cardiovascular biology Health sciences/Diseases/Cardiovascular diseases/Acute coronary syndromes Sleep disorders Myocardial infarction Mendelian randomization Colocalization analysis Single-cell analysis Full Text Additional Declarations No competing interests reported. Supplementary Files supplementaryfigure1.png supplementaryfigure2.png supplementaryfigure3.jpg SupplementaryTable.docx STROBEMRchecklistfillable3.docx Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 16 Jul, 2024 Editor invited by journal 18 Jun, 2024 Submission checks completed at journal 14 Jun, 2024 First submitted to journal 19 Apr, 2024 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4291368","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":320702058,"identity":"3b9f14b3-3d9e-4a2d-b443-49e0c9ba8625","order_by":0,"name":"Zhihuan Luo","email":"","orcid":"","institution":"Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research","correspondingAuthor":false,"prefix":"","firstName":"Zhihuan","middleName":"","lastName":"Luo","suffix":""},{"id":320702059,"identity":"8f8b5bd4-db07-4e2f-9687-39aa067cb188","order_by":1,"name":"Pan 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infarction","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sleep disorders, Myocardial infarction, Mendelian randomization, Colocalization analysis, Single-cell analysis","lastPublishedDoi":"10.21203/rs.3.rs-4291368/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4291368/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003eMyocardial infarction (MI) and sleep apnoea are common diseases, and epidemiologic evidence suggests that the two are related.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e Our research relied on genome-wide association summary statistics (GWAS) pertaining to patients diagnosed with sleep apnoea, snoring, insomnia, or narcolepsy, as well as individuals diagnosed with MI. Using a bidirectional Mendelian randomization (MR) approach, we investigated the relationships between MI and sleep apnoea, snoring, insomnia and narcolepsy. In addition, colocalization analysis was used to identify genes whose increased expression may contribute to sleep disorders. Subsequently, we illustrated that the upregulation of these genes serves as a negative prognostic factor for MI through the application of summary-data-based MR (SMR). Furthermore, we analysedsingle-cell data obtained from individuals with MI to elucidate the subcellular localization of these genes and assess the enriched pathways.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003eBidirectional MR analysis suggested no causal association between sleep apnoea and MI. Snoring, insomnia, and narcolepsy are risk factors for MI. The genes associated with snoring, insomnia, and narcolepsy were all colocalized with eQTLs. SMR demonstrated that these genes are risk factors for MI. Single-cell analysis revealed that these genes were predominantly localized to cardiac endothelial cells and enriched in the Rap1 pathway.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e Our study revealedthat snoring, insomnia, and narcolepsy are risk factors for MI. The primary mechanism could involve sleep disorders inducing alterations in the expression abundance of LINC02210, LRRC37A, LRRC37A2, KANSL1-AS1, and DND1P1, thereby increasing the risk of MI via the Rap1 pathway.\u003c/p\u003e","manuscriptTitle":"Mendelian randomization and single-cell analysis reveal relationships between sleep disorders and myocardial infarction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-01 06:06:24","doi":"10.21203/rs.3.rs-4291368/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-07-16T18:20:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-18T11:06:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-14T10:02:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-04-19T06:56:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"68140e73-736b-444a-874e-c02114d1d58a","owner":[],"postedDate":"July 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":33905878,"name":"Health sciences/Cardiology/Cardiovascular biology"},{"id":33905879,"name":"Health sciences/Diseases/Cardiovascular diseases/Acute coronary syndromes"}],"tags":[],"updatedAt":"2024-07-01T06:06:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-01 06:06:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4291368","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4291368","identity":"rs-4291368","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}