Integrating Variant Functional Annotation Scores Have Varied Abilities To Improve Power Of Genome-Wide Association Studies

Integrating Variant Functional Annotation Scores Have Varied Abilities To Improve Power Of Genome-Wide Association Studies | 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 Integrating Variant Functional Annotation Scores Have Varied Abilities To Improve Power Of Genome-Wide Association Studies Jianhui Gao, Osvaldo Espin-Garcia, Andrew D. Paterson, Lei Sun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1401415/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Functional annotations have the potential to increase power of genome-wide association studies (GWAS) by prioritizing variants according to their biological function, but this potential has not been well studied. We comprehensively evaluated all 1,132 traits in the UK Biobank whose SNP-heritability estimates were given "medium" or "high" labels by Neale’s lab. For each trait, we integrated GWAS summary statistics of close to 8 million common variants (minor allele frequency > 1%) with either their 75 individual functional scores or their meta-scores, using three different data-integration methods. Overall, the number of new genome-wide significant findings after data-integration increases as a trait SNP-heritability estimate increases. However, there is a trade-off between new findings and loss of baseline GWAS findings, resulting in similar total numbers of significant findings between using GWAS alone and integrating GWAS with functional scores, across all 1,132 traits analyzed and all three data-integration methods considered. Our findings suggest that, even with the current biobank-level sample size, more informative functional scores and/or new data-integration methods are needed to further improve power of GWAS of common variants. Full Text Additional Declarations No competing interests reported. Supplementary Files suppfigure.pdf supptable.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 25 Apr, 2022 Reviews received at journal 24 Apr, 2022 Reviewers agreed at journal 12 Apr, 2022 Reviews received at journal 12 Apr, 2022 Reviewers agreed at journal 02 Apr, 2022 Reviewers invited by journal 08 Mar, 2022 Editor assigned by journal 08 Mar, 2022 Editor invited by journal 05 Mar, 2022 Submission checks completed at journal 05 Mar, 2022 First submitted to journal 27 Feb, 2022 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-1401415","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":88487837,"identity":"d4c59531-85a8-43ff-afe2-f7fc9a3c9d36","order_by":0,"name":"Jianhui Gao","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianhui","middleName":"","lastName":"Gao","suffix":""},{"id":88487838,"identity":"15a292ce-53c3-4729-b2ba-2390ae9deec6","order_by":1,"name":"Osvaldo Espin-Garcia","email":"","orcid":"","institution":"University Health Network","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Osvaldo","middleName":"","lastName":"Espin-Garcia","suffix":""},{"id":88487839,"identity":"2f5bb3bf-6732-4f72-8072-8502858841ea","order_by":2,"name":"Andrew D. 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