Network-based analysis of genome-wide biobank data boosts discovery of genetic associations in psoriasis

Network-based analysis of genome-wide biobank data boosts discovery of genetic associations in psoriasis | 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 Network-based analysis of genome-wide biobank data boosts discovery of genetic associations in psoriasis Giann Karlo Aguirre-Samboní, Gwenaëlle Lemoine, Julio Molineros, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8700526/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Psoriasis is a common autoimmune disease with a strong genetic component. Targeting the \textit{IL-23/IL-17} pathways for the treatment of moderate-severe psoriasis has proven successful, which makes it a good benchmark for other drug discovery approaches. Genome Wide Association Studies (GWAS) identify genetic loci associated with a phenotype (e.g. disease). However, using identified loci to understand the disease mechanisms remains challenging. In response, gene networks methods that consider gene-gene relationships have been developed. In a previous study, we showed that the combination of network methods improved the power, reproducibility, and interpretability of those approaches on a small cohort of breast cancer patients. The goal of the present study is to benchmark the performance of the same combination of network methods on a psoriasis cohort from the UK biobank (with a particular interest on the \textit{IL-23/IL-17} pathways). By applying this method, we identified well known psoriasis genes, demonstrating the viability of our approach. Our method further identified a small set of genes of the MRPL family robustly associated with psoriasis, demonstrating that this approach can provide insights into the potential disease mechanisms. Our study also shows that our method is applicable to large-scale biobank data to produce novel findings, even in well-studied diseases with strong genetic signal. Network-based methods psoriasis biological networks GWAS Full Text Additional Declarations Competing interest reported. JM works at Johnson and Johnson Innovative Medicine, and part of our funding comes from Janssen Research & Development. Supplementary Files supplementarymaterialtables1aguirre2026.xlsx supplementarymaterialtables2aguirre2026.xlsx supplementarymaterialfiguresaguirre2026.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 25 Mar, 2026 Reviews received at journal 23 Mar, 2026 Reviews received at journal 18 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers invited by journal 13 Mar, 2026 Editor invited by journal 11 Mar, 2026 Editor assigned by journal 28 Jan, 2026 Submission checks completed at journal 28 Jan, 2026 First submitted to journal 26 Jan, 2026 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-8700526","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605900570,"identity":"5908b192-0cf9-4e15-a052-162f27ecf7aa","order_by":0,"name":"Giann Karlo Aguirre-Samboní","email":"data:image/png;base64,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","orcid":"","institution":"Mines Paris, PSL University","correspondingAuthor":true,"prefix":"","firstName":"Giann","middleName":"Karlo","lastName":"Aguirre-Samboní","suffix":""},{"id":605900572,"identity":"cf435a6b-6e42-404e-952b-c245fdaadf3d","order_by":1,"name":"Gwenaëlle Lemoine","email":"","orcid":"","institution":"Mines Paris, PSL University","correspondingAuthor":false,"prefix":"","firstName":"Gwenaëlle","middleName":"","lastName":"Lemoine","suffix":""},{"id":605900574,"identity":"fab35996-febc-4071-897f-2b7db12a9ddf","order_by":2,"name":"Julio Molineros","email":"","orcid":"","institution":"Johnson \u0026 Johnson (United States)","correspondingAuthor":false,"prefix":"","firstName":"Julio","middleName":"","lastName":"Molineros","suffix":""},{"id":605900577,"identity":"1c288b69-8821-4228-85d6-3166fda6034b","order_by":3,"name":"Florian Massip","email":"","orcid":"","institution":"Mines Paris, PSL University","correspondingAuthor":false,"prefix":"","firstName":"Florian","middleName":"","lastName":"Massip","suffix":""},{"id":605900590,"identity":"cc2e3d75-020c-4a0b-acf8-018618a04aee","order_by":4,"name":"Chloé-Agathe Azencott","email":"","orcid":"","institution":"Mines Paris, PSL University","correspondingAuthor":false,"prefix":"","firstName":"Chloé-Agathe","middleName":"","lastName":"Azencott","suffix":""}],"badges":[],"createdAt":"2026-01-26 13:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8700526/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8700526/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104785095,"identity":"9e91ff69-a0fa-460b-b045-9614c3ece24e","added_by":"auto","created_at":"2026-03-17 08:09:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3142119,"visible":true,"origin":"","legend":"","description":"","filename":"networkgwasbiobankpsoriasis.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8700526/v1_covered_7216864c-5f48-4373-84e0-e93bb7d88687.pdf"},{"id":104783234,"identity":"654b4277-a76f-4563-ad77-d6587b22d9d5","added_by":"auto","created_at":"2026-03-17 07:58:26","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":129194,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterialtables1aguirre2026.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8700526/v1/dbb88a3714db30d76f0f5e75.xlsx"},{"id":104748071,"identity":"e9dce38e-407f-4c6e-95f2-53e7ee8bf04d","added_by":"auto","created_at":"2026-03-16 18:34:40","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":168112,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterialtables2aguirre2026.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8700526/v1/c8a51dca5b57c5e47ee46b52.xlsx"},{"id":104748073,"identity":"3fba944a-7109-4c94-a38e-49d7693e3fc7","added_by":"auto","created_at":"2026-03-16 18:34:40","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1137297,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterialfiguresaguirre2026.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8700526/v1/bc77628e8fe3b198ff3e0c31.pdf"}],"financialInterests":"Competing interest reported. 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Targeting the \\textit{IL-23/IL-17} pathways for the treatment of moderate-severe psoriasis has proven successful, which makes it a good benchmark for other drug discovery approaches. Genome Wide Association Studies (GWAS) identify genetic loci associated with a phenotype (e.g. disease). However, using identified loci to understand the disease mechanisms remains challenging. In response, gene networks methods that consider gene-gene relationships have been developed. In a previous study, we showed that the combination of network methods improved the power, reproducibility, and interpretability of those approaches on a small cohort of breast cancer patients. The goal of the present study is to benchmark the performance of the same combination of network methods on a psoriasis cohort from the UK biobank (with a particular interest on the \\textit{IL-23/IL-17} pathways). By applying this method, we identified well known psoriasis genes, demonstrating the viability of our approach. Our method further identified a small set of genes of the MRPL family robustly associated with psoriasis, demonstrating that this approach can provide insights into the potential disease mechanisms. 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