Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans | 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 Diet-responsive proteogenomic effects following short-term restriction of animal products in humans Antigone Dimas, Alexandros Simistiras, Ozvan Bocher, Christina Emmanouil, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7213009/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 The effect of diet on genetic regulation in humans remains largely unexplored. Here, we investigated gene-by-diet interactions in a unique group of apparently healthy individuals (N=200) who alternate between omnivory and dietary restriction of animal products for religious reasons. Using longitudinal plasma proteomic and genotypic data, we identified diet-responsive cis-protein quantitative trait loci (cis-pQTLs) including gain of genetic regulatory effects for LBR and MSRA, proteins linked to cholesterol and methionine metabolism respectively. LBR-associated diet-responsive cis-pQTL rs74148404 showed suggestive evidence of colocalization with obesity exclusively under dietary restriction, suggesting diet-dependent differential genetic risk for disease. Additionally, a novel dietary restriction-associated cis-pQTL for metabolic regulator FGF21 colocalized with eosinophil and platelet traits pointing to diet-sensitive immunometabolic signalling. By parallel profiling of a continuously omnivorous control group (N=211), we also uncovered seasonally dynamic gain and loss of genetic regulation for proteins linked to apoptosis in immune system pathways (MAVS, CASP3, PDLIM7 IL12RB1), effects likely masked by animal product restriction. These findings reveal dynamic diet- and season-sensitive regulatory mechanisms with implications for precision nutrition and individualized disease prevention strategies, and underscore the need to integrate environmental context into genetic studies of health and disease. Biological sciences/Genetics/Functional genomics Biological sciences/Molecular biology/Proteomics Biological sciences/Genetics/Gene regulation Biological sciences/Genetics/Genetic association study Biological sciences/Genetics/Genetic interaction Full Text Additional Declarations There is NO Competing Interest. Supplementary Files pqtl.manuscript.supplement.docx Supplementary Data pqtl.manuscript.supplementary.tables.xlsx Supplementary Tables 2-7 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. 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-7213009","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":496732826,"identity":"312cd79d-a091-46f6-84f7-f93490642277","order_by":0,"name":"Antigone Dimas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDCCwyCiQk6GgYGxgRQtZ4x5SNByAIgZ20BaiAV8x7kTP/6cZ8DDL3a47eEXhtp8glokD/NulubdZsAjOTux3ViG4bglQecZHObdIM247Q+Pwe3ENmkJhmMGBG0Batn88+ccAx57UrRsk+BtMOAxkE5sk/zAUENYC9Av26x5jhnwSIBsYTA4QFgL3/mzm2/+qDGQ45+d/kzyR0UdYS0ogJnH4DBpOhgYfzDUkahlFIyCUTAKRgIAAGGqOYeyzQO5AAAAAElFTkSuQmCC","orcid":"","institution":"Biomedical Sciences Research Center Alexander Fleming","correspondingAuthor":true,"prefix":"","firstName":"Antigone","middleName":"","lastName":"Dimas","suffix":""},{"id":496732827,"identity":"1f783c51-74fe-4330-a7a5-65fd7b047747","order_by":1,"name":"Alexandros Simistiras","email":"","orcid":"https://orcid.org/0000-0002-7683-7400","institution":"Biomedical Sciences Research Center Alexander Fleming","correspondingAuthor":false,"prefix":"","firstName":"Alexandros","middleName":"","lastName":"Simistiras","suffix":""},{"id":496732828,"identity":"dc6f05c3-0de7-4f5b-a2eb-916e9d13cdbf","order_by":2,"name":"Ozvan Bocher","email":"","orcid":"https://orcid.org/0000-0002-2467-9236","institution":"Institute of Translational Genomics, Helmholtz Zentrum München - 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