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Here, we develop a method\u2014time-resolved Mendelian randomization\u2014to estimate the cumulative effect of body mass index on disease risk at different ages. Using the UK Biobank, we find strong age-varying patterns for type 2 diabetes mellitus, coronary artery disease, and atrial fibrillation, as well as for osteoarthritis. We demonstrate that some of the most notable temporal characteristics are sex specific, while other features are shared between sexes. Analyses suggest that these features can be manifestations of primary prevention strategies.<\/jats:p>","DOI":"10.1126\/sciadv.adv0926","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:58:36Z","timestamp":1761328716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Time-resolved Mendelian randomization detects substantial variation in the detrimental effect of obesity throughout life"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-6149","authenticated-orcid":true,"given":"Torgny","family":"Karlsson","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Box 815, 75108 Uppsala, 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