A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study

A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study | 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 Research Article A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study Zhen Chen, Shan Yao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6372861/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 Objective: Gout and Uric acid levels have been investigated in observational studies with epilepsy risk; however, the results were inconsistent. Therefore, we conducted a Mendelian randomization (MR) study to assess the causality of these relationships. Methods: To explore the causal relationship and ascertain specific Gout and Uric acid for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on data from the Epilepsy Genome-wide Association Study (GWAS) provided by the International League Against Epilepsy. The GWAS summary statistics for Gout were generated by the FINNGEN consortium and GWAS data of Uric acid from the Bio-Bank Japan (BBJ). The main analytical method for evaluating causality was the inverse-variance weighted (IVW) approach. To complement the IVW method, we also applied three additional MR methods: MR-Egger, and weighted median. Additionally, because the number of SNP-s screened out is relatively small in this study, so there may be weak instrumental variables, and MR-RAPS is a method that specifically deals with weak instrumental variables and exists to assist the results generated by IVW. Results: Genetically predicted Gout was associated with a higher risk of epilepsy (OR:1.014, CI:1.011-1.017, P<0.0001)、Generalized epilepsy (OR:1.009, CI:1.000-1.018, P=0.0424) and Focal epilepsy (OR:1.033, CI:1.002-1.088, P=0.0407)in the European populations. Genetically predicted Uric acid levels was not related to epilepsy、generalized epilepsy and focal epilepsy in Europe and Gout and Uric acid levels were not related to epilepsy in East Asia. Our results suggest that gout has a detrimental effect on epilepsy risk、sensitivity analyses found no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusions: This is the first study to explore the potential causal relationship between gout、uric acid and epilepsy using MR Analysis. Through the MR study, we analyzed the causal relationship between gout and uric acid and epilepsy and identified specific ones associated with an increased risk of epilepsy. Our findings may provide useful biomarkers for disease progression in epilepsy and candidates for potential therapeutic targets. In addition, our study highlights the importance of conducting genetic association studies in diverse populations to fully understand the genetic and environmental interactions of complex diseases. Gout Uric acid epilepsy risk Mendelian randomization Full Text Additional Declarations No competing interests reported. Supplementary Files STROBEMRchecklistfillableApril182025.pdf 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. 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-6372861","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":452563679,"identity":"0f5057f9-1761-4d20-b234-af533981e7fa","order_by":0,"name":"Zhen Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBAC+xlA4oeBDQ8/e2Pjgw/EaGEEamHsqUiTk+w53Gw4g1gtzCxnDhsb3Ehvk+YgRguzdPOxx4xtaYkzZz5skGZgsJPTbSCghU3mWLoxY5tNYr90YoNxAUOysdkBAlp4JHLMpMG2zE5sSJ7BcCBxGyEtEhL534BaDiduuHmw4TAPMVoMJHLYpCHeZ2xsJlJLmpkkJJATmxlnGBDhF/sZyc8kIFF5/PmPDxV2cgS1oFtKmvJRMApGwSgYBTgAALKRRIypeJf/AAAAAElFTkSuQmCC","orcid":"","institution":"The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)","correspondingAuthor":true,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Chen","suffix":""},{"id":452563680,"identity":"d93f83c5-85bd-49ba-9a87-79b05711674b","order_by":1,"name":"Shan Yao","email":"","orcid":"","institution":"The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)","correspondingAuthor":false,"prefix":"","firstName":"Shan","middleName":"","lastName":"Yao","suffix":""}],"badges":[],"createdAt":"2025-04-04 03:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6372861/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6372861/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89545626,"identity":"1786094e-eaf4-4180-b36c-143f2e33f63e","added_by":"auto","created_at":"2025-08-21 07:17:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1463078,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptApril182025.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6372861/v1_covered_2043f928-4344-4793-921b-17a08ab80817.pdf"},{"id":82315702,"identity":"13c56631-f99f-4f64-9f7c-b5b3d36808d8","added_by":"auto","created_at":"2025-05-09 03:23:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":145828,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEMRchecklistfillableApril182025.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6372861/v1/ba77995adfb5bb6f4c3d6d5e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Gout, Uric acid, epilepsy, risk, Mendelian randomization","lastPublishedDoi":"10.21203/rs.3.rs-6372861/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6372861/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: Gout and Uric acid levels have been investigated in observational studies with epilepsy risk; however, the results were inconsistent. Therefore, we conducted a Mendelian randomization (MR) study to assess the causality of these relationships.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods: To explore the causal relationship and ascertain specific Gout and Uric acid for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on data from the Epilepsy Genome-wide Association Study (GWAS) provided by the International League Against Epilepsy. The GWAS summary statistics for Gout were generated by the FINNGEN consortium and GWAS data of Uric acid from the Bio-Bank Japan (BBJ). The main analytical method for evaluating causality was the inverse-variance weighted (IVW) approach. To complement the IVW method, we also applied three additional MR methods: MR-Egger, and weighted median. Additionally, because the number of SNP-s screened out is relatively small in this study, so there may be weak instrumental variables, and MR-RAPS is a method that specifically deals with weak instrumental variables and exists to assist the results generated by IVW.\u003c/p\u003e\n\u003cp\u003eResults: Genetically predicted Gout was associated with a higher risk of epilepsy (OR:1.014, CI:1.011-1.017, P\u0026lt;0.0001)、Generalized epilepsy (OR:1.009, CI:1.000-1.018, P=0.0424) and Focal epilepsy (OR:1.033, CI:1.002-1.088, P=0.0407)in the European populations. Genetically predicted Uric acid levels was not related to epilepsy、generalized epilepsy and focal epilepsy in Europe and Gout and Uric acid levels were not related to epilepsy in East Asia. Our results suggest that gout has a detrimental effect on epilepsy risk、sensitivity analyses found no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity.\u003c/p\u003e\n\u003cp\u003eConclusions: This is the first study to explore the potential causal relationship between gout、uric acid and epilepsy using MR Analysis. Through the MR study, we analyzed the causal relationship between gout and uric acid and epilepsy and identified specific ones associated with an increased risk of epilepsy. Our findings may provide useful biomarkers for disease progression in epilepsy and candidates for potential therapeutic targets. In addition, our study highlights the importance of conducting genetic association studies in diverse populations to fully understand the genetic and environmental interactions of complex diseases.\u003c/p\u003e","manuscriptTitle":"A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 03:23:45","doi":"10.21203/rs.3.rs-6372861/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3e565fc1-c475-493e-8de2-93328cf4a107","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-21T07:09:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 03:23:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6372861","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6372861","identity":"rs-6372861","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}