Genetic architecture of adaptive immune responses and adverse reactions to inactivated COVID-19 vaccine

Genetic architecture of adaptive immune responses and adverse reactions to inactivated COVID-19 vaccine | 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 architecture of adaptive immune responses and adverse reactions to inactivated COVID-19 vaccine Zijie Zhang, Tianpei Shi, Fengwei Liu, Yajing Wang, Na Wan, Huajie Hu, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7033863/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Host genetic determinants influence vaccine efficacy. The majority of participants in current COVID-19 vaccine genetic studies are of European ancestry, and the basis for individual differences in cell phenotypes is largely unclear. Here, we report a genome-wide association study (GWAS) of comprehensive vaccine response, encompassing humoral immunity, cellular immunity and adverse reactions, in 2,299 Chinese individuals vaccinated with CoronaVac or BBIBP-CorV. We identify 14 fine-mapped genetic variants significantly associated with adaptive immune response and reactogenicity. Among them, 12 represent previously unreported loci and 2 (rs140176526 and rs11262794) are putative regulatory variants by Bayesian colocalization. SNP-based heritability is substantial for humoral immunity (33.4%). Integrating GWAS data with single-nucleus ATAC-seq (snATAC) and single-nucleus RNA-seq (snRNA) co-assay profiles across 10 time points identifies trait-associated immune cell types. Notably, MAIT and NKT show significant partitioned heritability enrichments across all phenotypes including neutralizing antibody (NAb) responses, T-helper 1 (Th1) cells responses, B cell memory, fatigue and muscle pain. Our findings unveil previously unrecognized genomic factors and epigenomic regulatory mechanisms underlying individual variability in vaccine responses at high resolution. Biological sciences/Genetics/Genetic association study/Genome-wide association studies Biological sciences/Genetics Full Text Additional Declarations Yes there is potential Competing Interest. ZJZ served as a PI in a phase 4 clinical study sponsored by Sinovac Biotech Ltd. The funder has no role in study design, implementation and manuscript writing in this study. Supplementary Files SupplementaryMaterial.pdf Genetic architecture of adaptive immune responses and adverse reactions to inactivated COVID-19 vaccine Cite Share Download PDF Status: Posted 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-7033863","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":483460817,"identity":"d6f468bf-6cb2-4927-8a33-82d7208be2d9","order_by":0,"name":"Zijie 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The majority of participants in current COVID-19 vaccine genetic studies are of European ancestry, and the basis for individual differences in cell phenotypes is largely unclear. Here, we report a genome-wide association study (GWAS) of comprehensive vaccine response, encompassing humoral immunity, cellular immunity and adverse reactions, in 2,299 Chinese individuals vaccinated with CoronaVac or BBIBP-CorV. We identify 14 fine-mapped genetic variants significantly associated with adaptive immune response and reactogenicity. Among them, 12 represent previously unreported loci and 2 (rs140176526 and rs11262794) are putative regulatory variants by Bayesian colocalization. SNP-based heritability is substantial for humoral immunity (33.4%). Integrating GWAS data with single-nucleus ATAC-seq (snATAC) and single-nucleus RNA-seq (snRNA) co-assay profiles across 10 time points identifies trait-associated immune cell types. Notably, MAIT and NKT show significant partitioned heritability enrichments across all phenotypes including neutralizing antibody (NAb) responses, T-helper 1 (Th1) cells responses, B cell memory, fatigue and muscle pain. 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