Exposure to maternal human milk components interacts with infant polygenic risk to predict childhood atopy

Exposure to maternal human milk components interacts with infant polygenic risk to predict childhood atopy | 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 Exposure to maternal human milk components interacts with infant polygenic risk to predict childhood atopy Qingling Duan, Zhi Yi Fang, Sara Stickley, Jihoon Choi, Elizabeth George, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7143108/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 Although human milk (HM) is known to benefit infant health, how its many bioactive components (e.g., microbiota (HMM), oligosaccharides (HMOs), and fatty acids (HMFAs)) influence the risk of childhood atopy remains poorly understood. Our study integrated polygenic risk scores (PRS) of nursing infants with human milk components (HMCs) from their mothers in the CHILD Cohort Study to explore potential gene-milk interactions associated with childhood atopy at ages 1-5. For example, among infants with high PRS, exposure to increased abundance of the microbe Abiotrophia was associated with increased childhood atopy prevalence. Moreover, network analyses combining all HMCs revealed that a module of correlated HMM and HMOs including Abiotrophia and 3-fucosyllactose, respectively, was associated with reduced childhood atopy prevalence. Another network module of correlated HMCs (e.g., Bifidobacterium longum, 2'-fucosyllactose, and eicosapentaenoic acid) was associated with reduced childhood atopy prevalence among infants with high PRS. Finally, a gradient-boosting model (GBM) integrating HMCs and infant PRS predicted childhood atopy with an area under the curve (AUC) of 0.78, outperforming GBMs using any individual HMC or infant PRS alone (AUC range: 0.48-0.63). Our study reports both main and interaction effects of HMCs and infant PRS on childhood atopy. An improved understanding of how early-life exposures such as HMCs impact the health of children differently depending on their genomic profiles may facilitate the development of personalized intervention strategies to reduce the burden of these health outcomes during childhood. Health sciences/Medical research/Genetics research Health sciences/Risk factors Biological sciences/Computational biology and bioinformatics/Predictive medicine Biological sciences/Systems biology/Genetic interaction Full Text Additional Declarations Yes there is potential Competing Interest. Jihoon Choi is currently an employee of F. Hoffmann-La Roche Ltd.; however, the published work does not involve or endorse any materials or viewpoints of Roche. Supplementary Files SI.pdf Supplemental Material 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-7143108","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":489345508,"identity":"5b67c915-a432-4c22-a5ce-a8de18518b33","order_by":0,"name":"Qingling Duan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYDACZiB+YABiJQBxBbFaEuBazhBrUwKMZGwjQjXfcd7DLxIK7tg1sOcYfi6cZ53Yz957+DMPg508Li2Sh/nSLBIMniU38Lwxlp65LT1xZs+5NGkehmTDBhxaDA7zmBkkGBxOZpDIMZDm3XY4ccONHDNmHoYDjMRoMf7NO+dw4v77b4yBDjtgj0eL8QOgFjugFjNp3gagLRI8BkCHHUjEpUUSaAswkA8nsPE8K7PmOZZuPONMjpnkHIPkZFxa+M6fMf7w4c9he3725M23eWqsZfvbgSJvKuxscWlhOMDAJgGkEqExwgxzMC71YC3MH4CUPQOqllEwCkbBKBgFCAAAuxBVXeaHYh4AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-4467-7024","institution":"Queen's University","correspondingAuthor":true,"prefix":"","firstName":"Qingling","middleName":"","lastName":"Duan","suffix":""},{"id":489345509,"identity":"a6e10111-b56e-4fa9-830b-0ea89ae8d181","order_by":1,"name":"Zhi Yi Fang","email":"","orcid":"https://orcid.org/0009-0000-1945-9258","institution":"Queen's University","correspondingAuthor":false,"prefix":"","firstName":"Zhi","middleName":"Yi","lastName":"Fang","suffix":""},{"id":489345510,"identity":"d3f9baf8-5fe2-464b-b9f6-468a6b4ff0ac","order_by":2,"name":"Sara Stickley","email":"","orcid":"https://orcid.org/0009-0003-7958-4650","institution":"Queens University","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Stickley","suffix":""},{"id":489345511,"identity":"28157f99-ff52-490a-96a6-b1189c487d27","order_by":3,"name":"Jihoon Choi","email":"","orcid":"","institution":"Queens University","correspondingAuthor":false,"prefix":"","firstName":"Jihoon","middleName":"","lastName":"Choi","suffix":""},{"id":489345512,"identity":"4315675e-110a-4fc7-8eea-2f9799953b1b","order_by":4,"name":"Elizabeth George","email":"","orcid":"","institution":"Queen's University","correspondingAuthor":false,"prefix":"","firstName":"Elizabeth","middleName":"","lastName":"George","suffix":""},{"id":489345513,"identity":"9a001a9b-f5f3-499b-a924-0607e977498c","order_by":5,"name":"Joel Sagman","email":"","orcid":"","institution":"Queen's University","correspondingAuthor":false,"prefix":"","firstName":"Joel","middleName":"","lastName":"Sagman","suffix":""},{"id":489345514,"identity":"a5ea3324-32b3-458d-a21d-05183cf60fe0","order_by":6,"name":"Amanda Zacharias","email":"","orcid":"https://orcid.org/0000-0002-5598-0232","institution":"Queen's University","correspondingAuthor":false,"prefix":"","firstName":"Amanda","middleName":"","lastName":"Zacharias","suffix":""},{"id":489345515,"identity":"33995f60-35b2-452a-bff0-9772446ab8a5","order_by":7,"name":"Amirthagowri Ambalavanan","email":"","orcid":"","institution":"Queen's University","correspondingAuthor":false,"prefix":"","firstName":"Amirthagowri","middleName":"","lastName":"Ambalavanan","suffix":""},{"id":489345516,"identity":"ab9f9522-d20d-479c-8eba-5394a49572b0","order_by":8,"name":"Shirin Moossavi","email":"","orcid":"","institution":"University of Manitoba","correspondingAuthor":false,"prefix":"","firstName":"Shirin","middleName":"","lastName":"Moossavi","suffix":""},{"id":489345517,"identity":"4eff34b2-84ac-4f5a-8a6c-69d874af9cb5","order_by":9,"name":"Charisse Petersen","email":"","orcid":"","institution":"Department of Pediatrics, BC Children’s Hospital, University of British Columbia; 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