Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures

Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures | 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 Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures Laura Raffield, Jayna Nicholas, Daniel Katz, Usman Tahir, Catherine Debban, and 47 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5968391/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.30). Protein measures were associated with variants (pQTLs), and one-third of the pQTL signals were driven by protein-altering variants (PAVs). We highlight 80 proteins that correlate differently across ancestry groups likely due to differing PAV frequencies by ancestry. Furthermore, adjustment for PAVs with opposite directions of effect by platform improved inter-platform protein measure correlation and resulted in more concordant genetic and phenotypic associations. Hence, PAVs need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement. Biological sciences/Genetics Health sciences/Risk factors Full Text Additional Declarations Yes there is potential Competing Interest. LMR is a consultant for the TOPMed Administrative Coordinating Center (through Westat). DG is the Chief Executive Officer of Sequoia Genetics, a private company that works with investors, pharma, biotech, and academia by performing research that leverages genetic data to help inform drug discovery and development. DG has interests in several biotech companies. Supplementary Files SupplementaryInformation.pdf Supplementary Notes and Supplementary Figures TablesandSupplementalTables.xlsx Main Tables 1-2, Supplementary Tables 1-26, Extended Data Tables 1-6 Cite Share Download PDF Status: Published Journal Publication published 22 Jan, 2026 Read the published version in Nature Communications → 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-5968391","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":415008628,"identity":"c5e6b264-5d06-4e60-a0b0-e49f6bfee5c4","order_by":0,"name":"Laura 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DG has interests in several biotech companies.","formattedTitle":"Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5968391/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5968391/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.30). Protein measures were associated with variants (pQTLs), and one-third of the pQTL signals were driven by protein-altering variants (PAVs). We highlight 80 proteins that correlate differently across ancestry groups likely due to differing PAV frequencies by ancestry. Furthermore, adjustment for PAVs with opposite directions of effect by platform improved inter-platform protein measure correlation and resulted in more concordant genetic and phenotypic associations. Hence, PAVs need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.","manuscriptTitle":"Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-13 04:58:42","doi":"10.21203/rs.3.rs-5968391/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6eb13765-e1cb-4be6-8e4d-82fcbea59dba","owner":[],"postedDate":"February 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":44254972,"name":"Biological sciences/Genetics"},{"id":44254973,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-01-29T08:25:49+00:00","versionOfRecord":{"articleIdentity":"rs-5968391","link":"https://doi.org/10.1038/s41467-025-67814-1","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2026-01-22 05:00:00","publishedOnDateReadable":"January 22nd, 2026"},"versionCreatedAt":"2025-02-13 04:58:42","video":"","vorDoi":"10.1038/s41467-025-67814-1","vorDoiUrl":"https://doi.org/10.1038/s41467-025-67814-1","workflowStages":[]},"version":"v1","identity":"rs-5968391","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5968391","identity":"rs-5968391","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}