Familial co-aggregation and shared heritability between clinically diagnosed neurodevelopmental problems and cardiometabolic conditions: a nationwide register study across three generations

Familial co-aggregation and shared heritability between clinically diagnosed neurodevelopmental problems and cardiometabolic conditions: a nationwide register study across three generations | 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 Familial co-aggregation and shared heritability between clinically diagnosed neurodevelopmental problems and cardiometabolic conditions: a nationwide register study across three generations Yiran Li, Yiling Zhou, Melissa Vos, Martje Bos, Olivier Steen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6048644/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Nov, 2025 Read the published version in Nature Mental Health → Version 1 posted You are reading this latest preprint version Abstract Neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD) and autism co-occur with cardiometabolic conditions. However, little is known about the mechanisms underlying this co-occurrence. In this nationwide three-generation study using population-based registers in the Netherlands (n=15 million), we assessed the familial (co-)aggregation of ADHD, autism, and cardiometabolic conditions, and estimated their heritabilities and genetic correlations. ADHD, autism, and cardiometabolic conditions showed aggregation and co-aggregation within families and between spouses. Estimated heritabilities of ADHD and autism were moderate (both〖 h〗^2=0.5), while those of cardiometabolic conditions ranged from low to moderate (h^2=0.1-0.4). Genetic correlations between neurodevelopmental and cardiometabolic conditions were modest (r_g=–0.02-0.20). Together, these results suggest a partly shared familial liability for neurodevelopmental and cardiometabolic conditions, and environmental factors likely play a more important role in the co-occurrence of neurodevelopmental and cardiometabolic conditions than genetics. These new insights can advance research toward specific etiological mechanisms and inform preventive strategies. Health sciences/Medical research/Epidemiology Health sciences/Diseases/Cardiovascular diseases Health sciences/Health care/Public health Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementMaterials.pdf Supplementary Figures and Methods SupplementTables.pdf Supplementary Tables Cite Share Download PDF Status: Published Journal Publication published 03 Nov, 2025 Read the published version in Nature Mental Health → 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. 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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-6048644","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":497701716,"identity":"292bae35-619e-4659-acd1-833194386fcf","order_by":0,"name":"Yiran 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