Identification of Circadian Rhythm-Associated Genes and Therapeutic Targets in Myopia with Dynamics Simulation: A Multiomics Study Using Machine Learning Algorithms and Mendelian Randomization

Identification of Circadian Rhythm-Associated Genes and Therapeutic Targets in Myopia with Dynamics Simulation: A Multiomics Study Using Machine Learning Algorithms and Mendelian Randomization | 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 Identification of Circadian Rhythm-Associated Genes and Therapeutic Targets in Myopia with Dynamics Simulation: A Multiomics Study Using Machine Learning Algorithms and Mendelian Randomization Jiahao Niu, Jia Lin, Xianmei Zhou, Bowen Chen, Yuanyuan Hu, Qingqing Tan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6821540/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Journal of Computer-Aided Molecular Design → Version 1 posted 9 You are reading this latest preprint version Abstract The prevalence of myopia is rising, with genetic and environmental factors playing key roles. Disruptions in circadian melatonin rhythms are also linked to refractive errors, though exact mechanisms remain unclear. Differential expression analysis on the GSE136701 dataset identified circadian-related genes. GSEA, GO, and KEGG analyses revealed key genes. To identify key genes, seven machine learning models were employed, and their performance was evaluated using ROC curve analysis. The correlation genes were further assessed. Concurrently, we performed a comprehensive analysis of immune infiltration and correlation pertaining to these pivotal genes. Additionally, potential target drugs were screened using the DSigDB database, and both protein-protein and molecular docking analyses were performed. To investigate the causal relationship between target genes and myopia, two-sample MR analysis was conducted. Finally, single-cell annotation and cell-cell communication analyses were carried out on the GSE235684 dataset. We preliminarily identified four circadian rhythm-related key genes: UTS2, BTBD9, S100A3, and LGALS9. We identified 8-Bromo-cAMP as the small molecule exhibiting the highest binding efficiency to BTBD9 and UTS2, with a docking binding energy of -37.5 kcal/mol for the BTBD9-UTS2 complex and -6.8 kcal/mol for the complex-small molecule interaction. The dynamics simulation analysis has further corroborated the dynamic stability of the UTS2-BTBD9 complex binding with 8-bromo-cAMP. Additionally, Mendelian randomization analysis revealed a significant association between UTS2 and myopia, with an inverse variance weighted (IVW) P value of 0.013 (OR 0.532, 95% CI 0.323-0.877). circadian rhythm myopia multiomics analysis machine learning immune infiltration molecular docking molecular dynamics simulation mendelian randomization Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Journal of Computer-Aided Molecular Design → Version 1 posted Editorial decision: Revision requested 12 Oct, 2025 Reviews received at journal 12 Oct, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviews received at journal 10 Jul, 2025 Reviewers agreed at journal 08 Jul, 2025 Reviewers invited by journal 18 Jun, 2025 Editor assigned by journal 18 Jun, 2025 Submission checks completed at journal 06 Jun, 2025 First submitted to journal 04 Jun, 2025 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. 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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-6821540","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":473199387,"identity":"c9850cc1-2f57-413e-ad7b-1f01b393c089","order_by":0,"name":"Jiahao Niu","email":"","orcid":"","institution":"North Sichuan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiahao","middleName":"","lastName":"Niu","suffix":""},{"id":473199389,"identity":"b32af173-6cc8-4b14-bf87-359b615ccb8b","order_by":1,"name":"Jia Lin","email":"","orcid":"","institution":"North Sichuan Medical 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