Examining the heritability of functional brain networks in adolescence

Examining the heritability of functional brain networks in adolescence | 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 Examining the heritability of functional brain networks in adolescence Christian Coffman, Sanju Koirala, Robert Hermosillo, Jacob Lundquist, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7632778/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 Understanding the mechanisms underlying mental illness requires disentangling the roles of genetic and environmental factors. The brain has been proposed as a key intermediate biomarker linking these factors, yet the extent to which genetics shapes adolescent brain function remains elusive. Using data from the ABCD study (5,247 unrelated, 330 dizygotic, 248 monozygotic twin participants), we estimated heritability of functional connectivity and topography using both SNP and twin data. SNP heritability, calculated using genetic correlation and the AdjHE-RE estimator, was low for connectivity (median = 2e-10% Gordon, 5.8e-7% probabilistic) and topography (max = 2%). Twin-based ACE models replicated prior literature (median = 8.9e-6% Gordon, 6% probabilistic connectivity, 27% topography). These results indicate that additive genetic effects have minimal influence on adolescent functional brain features, emphasizing the need to integrate environmental factors when studying the development of functional brain networks and their relevance to mental health. Biological sciences/Genetics/Heritable quantitative trait Biological sciences/Psychology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files functionaltopoheritSI.pdf Supplementary Information 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-7632778","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":520088584,"identity":"c0331b6f-73b4-4d24-8c13-06f9e8b0f53e","order_by":0,"name":"Christian Coffman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYFACxgcfGAzY5PghPGZitDAbzmCo4DOWbCBNyxm5xA0HiNXC397M2HSzzSxx843stAcMFdaJDYS0SJw5zNic25ZmvO1G7nYDhjPphLUYSOQff5zbdkwWqGWbBGPbYWK0JINs+c+4eQZIyz9iteScYVPcIAHS0kCEFrBfcirYjCXOvN0mkXAs3ZigFlCINeeAorIdaMuHGmtZglpQQQJpykfBKBgFo2AU4AIARvFAF64MPgwAAAAASUVORK5CYII=","orcid":"","institution":"University of Minnesota","correspondingAuthor":true,"prefix":"","firstName":"Christian","middleName":"","lastName":"Coffman","suffix":""},{"id":520088585,"identity":"99a41dd7-3cf5-4a40-a9a9-3e5e5d931b3b","order_by":1,"name":"Sanju Koirala","email":"","orcid":"","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Sanju","middleName":"","lastName":"Koirala","suffix":""},{"id":520088586,"identity":"fe8db691-5ee3-4987-aac3-8fad607be57a","order_by":2,"name":"Robert Hermosillo","email":"","orcid":"https://orcid.org/0000-0003-2959-8483","institution":"Masonic Institute for the Developing Brain, University of Minnesota Medical School","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Hermosillo","suffix":""},{"id":520088587,"identity":"f2ce4640-1e3f-4889-9e6b-2b68cdb5d794","order_by":3,"name":"Jacob Lundquist","email":"","orcid":"https://orcid.org/0000-0001-9573-1954","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Jacob","middleName":"","lastName":"Lundquist","suffix":""},{"id":520088588,"identity":"45579459-931e-4a34-83a8-5bce1a78bfc7","order_by":4,"name":"Gracie Grimsrud","email":"","orcid":"","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Gracie","middleName":"","lastName":"Grimsrud","suffix":""},{"id":520088589,"identity":"fba39133-b9b3-43f1-ad75-494abc9aa497","order_by":5,"name":"Oscar Miranda Dominguez","email":"","orcid":"https://orcid.org/0000-0002-3622-0166","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Oscar","middleName":"Miranda","lastName":"Dominguez","suffix":""},{"id":520088590,"identity":"5237cdee-dd02-4c3b-a071-98ebbe0276c6","order_by":6,"name":"Kimberly Weldon","email":"","orcid":"","institution":"University of Minnesota Medical School","correspondingAuthor":false,"prefix":"","firstName":"Kimberly","middleName":"","lastName":"Weldon","suffix":""},{"id":520088591,"identity":"8b6fcad4-4f34-4579-a9c0-2bea996eafad","order_by":7,"name":"Michael Anderson","email":"","orcid":"","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Anderson","suffix":""},{"id":520088592,"identity":"49887b28-f97e-4237-ab5d-c8c360f06001","order_by":8,"name":"Thomas Madison","email":"","orcid":"https://orcid.org/0000-0003-3030-6580","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Madison","suffix":""},{"id":520088593,"identity":"905ab377-e1ad-4631-b23e-23641148ab02","order_by":9,"name":"Steven Nelson","email":"","orcid":"","institution":"University of Minnesota Medical School","correspondingAuthor":false,"prefix":"","firstName":"Steven","middleName":"","lastName":"Nelson","suffix":""},{"id":520088594,"identity":"90d8054e-ac16-4fb9-aeee-9a59374bcda5","order_by":10,"name":"Jed Elison","email":"","orcid":"https://orcid.org/0000-0002-6246-1000","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Jed","middleName":"","lastName":"Elison","suffix":""},{"id":520088595,"identity":"f49eb5c2-9240-41fe-ae66-276922e49f8a","order_by":11,"name":"Sylia Wilson","email":"","orcid":"","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Sylia","middleName":"","lastName":"Wilson","suffix":""},{"id":520088596,"identity":"800535cd-96e1-4165-88b5-3ff12587721a","order_by":12,"name":"Damien Fair","email":"","orcid":"https://orcid.org/0000-0001-8602-393X","institution":"[email protected]","correspondingAuthor":false,"prefix":"","firstName":"Damien","middleName":"","lastName":"Fair","suffix":""},{"id":520088597,"identity":"37a79eab-aecc-4a60-a6eb-f6029a953d62","order_by":13,"name":"Brenden Tervo-Clemmens","email":"","orcid":"https://orcid.org/0000-0002-9557-1126","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Brenden","middleName":"","lastName":"Tervo-Clemmens","suffix":""},{"id":520088598,"identity":"499af624-46e7-4d05-adaa-68e91c5b77f7","order_by":14,"name":"Saonli Basu","email":"","orcid":"","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Saonli","middleName":"","lastName":"Basu","suffix":""},{"id":520088599,"identity":"5a312554-f090-4090-8811-c79bcfb351c1","order_by":15,"name":"Eric Feczko","email":"","orcid":"https://orcid.org/0000-0003-1337-5517","institution":"University of Minnesota","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"","lastName":"Feczko","suffix":""}],"badges":[],"createdAt":"2025-09-16 17:05:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7632778/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7632778/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94863774,"identity":"5482b553-0044-4d47-888b-60d4580c3466","added_by":"auto","created_at":"2025-10-31 13:37:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1937139,"visible":true,"origin":"","legend":"","description":"","filename":"HeritabilityPaperDraftX1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7632778/v1/48b5971f117425e3b8b1a44c.pdf"},{"id":94986099,"identity":"8cd0fd11-7bdc-4b8b-84b0-298caa3bcc3b","added_by":"auto","created_at":"2025-11-03 06:59:47","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":14586,"visible":true,"origin":"","legend":"","description":"","filename":"NCOMMS2568844.json","url":"https://assets-eu.researchsquare.com/files/rs-7632778/v1/dad57345cad368e34e413a4d.json"},{"id":94863775,"identity":"e7f5507e-15f3-48d3-8e22-5cd0c3227103","added_by":"auto","created_at":"2025-10-31 13:37:36","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2281153,"visible":true,"origin":"","legend":"","description":"","filename":"functionaltopoheritSI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7632778/v1/13f8bd22d5f9ef5b30d56f23.pdf"},{"id":94990486,"identity":"ac8141c0-0825-4175-ac60-853f62ac510b","added_by":"auto","created_at":"2025-11-03 07:17:25","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":913700,"visible":true,"origin":"","legend":"Article File","description":"","filename":"HeritabilityPaperDraftX1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7632778/v1_covered_7634cef6-679a-4934-a9c5-f6ecbe203a1c.pdf"},{"id":94863772,"identity":"7968ffec-c8d6-4a26-a334-78963798f378","added_by":"auto","created_at":"2025-10-31 13:37:36","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2281153,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"functionaltopoheritSI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7632778/v1/0fa04d799961752a82300bd2.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Examining the heritability of functional brain networks in adolescence","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"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-7632778/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7632778/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Understanding the mechanisms underlying mental illness requires disentangling the roles of genetic and environmental factors. The brain has been proposed as a key intermediate biomarker linking these factors, yet the extent to which genetics shapes adolescent brain function remains elusive. Using data from the ABCD study (5,247 unrelated, 330 dizygotic, 248 monozygotic twin participants), we estimated heritability of functional connectivity and topography using both SNP and twin data. SNP heritability, calculated using genetic correlation and the AdjHE-RE estimator, was low for connectivity (median = 2e-10% Gordon, 5.8e-7% probabilistic) and\r\ntopography (max = 2%). Twin-based ACE models replicated prior literature (median = 8.9e-6% Gordon, 6% probabilistic connectivity, 27% topography). These results indicate that additive genetic effects have minimal influence on adolescent functional brain features, emphasizing the need to integrate environmental factors when studying the development of functional brain networks and their relevance to mental health.","manuscriptTitle":"Examining the heritability of functional brain networks in adolescence","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-31 13:37:31","doi":"10.21203/rs.3.rs-7632778/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-biology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsbio","sideBox":"Learn more about [Communications Biology](http://www.nature.com/commsbio/)","snPcode":"","submissionUrl":"","title":"Communications Biology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"47625c81-a0f7-4681-9418-927bb998b16e","owner":[],"postedDate":"October 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":55281921,"name":"Biological sciences/Genetics/Heritable quantitative trait"},{"id":55281922,"name":"Biological sciences/Psychology"}],"tags":[],"updatedAt":"2025-10-31T13:37:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-31 13:37:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7632778","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7632778","identity":"rs-7632778","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}