Genetic Factor Analysis for Characterizing Phenome-Wide Patterns of Genetic Pleiotropy

Genetic Factor Analysis for Characterizing Phenome-Wide Patterns of Genetic Pleiotropy | 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 Genetic Factor Analysis for Characterizing Phenome-Wide Patterns of Genetic Pleiotropy Jean Morrison, Jason Willwerscheid, Dhajanae Sylvertooth, Xin He, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4714610/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Genetic associations shared by multiple traits provide evidence about the biological role of disease associated variants. We propose Genetic Factor Analysis (GFA), a multi-phenotype analysis method that identifies common patterns of cross-trait associations, the signatures of shared biological processes. GFA overcomes many limitations of alternative methods by automatically selecting the number of factors, accounting for sample overlap, and allowing factors to be non-orthogonal. We apply GFA to analysis of 22 common risk factors for coronary artery disease (CAD), and type 2 diabetes (T2D), allowing us to partition the heritability of CAD, T2D, and risk factors into 13 pleiotropic components. This analysis reveals, among other findings, that about 8% of the heritability of BMI is mediated by factors that do not contribute do CAD or T2D risk. In a second application, we use GFA to obtain a biologically meaningful decomposition of a large set of blood cell composition phenotypes and show that accounting for overlapping samples is critical to obtaining this result. Biological sciences/Genetics/Genetic association study/Genome-wide association studies Health sciences/Medical research/Genetics research Physical sciences/Mathematics and computing/Statistics Physical sciences/Mathematics and computing/Software Full Text Additional Declarations There is NO Competing Interest. Supplementary Files S1metabtraits1andbcpubinfo.csv S2mrresults.csv natgensupp.pdf Cite Share Download PDF Status: Under Review 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. 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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-4714610","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":329106341,"identity":"446ad972-da37-4ba3-bb89-2c9fa46a3dc0","order_by":0,"name":"Jean 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