Atlas of the Human Brain Imaging-derived Phenotypes and Disease Risk

Leveraging multimodal magnetic resonance imaging (MRI) and linked health records from 64,785 participants, we assessed associations between 505 brain imaging-derived phenotypes (IDPs)—including T1-weighted, diffusion, and resting-state functional MRI measures—and 738 incident diseases, establishing the largest atlas of brain–disease risk to date. Across 370,000 tests, 1,491 significant IDP–disease pairs were identified, revealing that brain alterations relate not only to neurological but also to peripheral conditions such as circulatory, digestive, and metabolic disorders. Clustering and network analyses highlighted white matter-related IDPs as a central hub linking brain and multisystem health. Prediction models combining IDPs with clinical covariates improved disease discrimination, and Mendelian randomization suggested causal roles of white matter-related IDPs in cerebrovascular disorders. This work advances mechanistic studies of brain–body interactions, cross-system risk assessment, and the translation of neuroimaging insights into therapeutic strategies. All associations are available in the Brain Imaging–Disease Atlas (www.brainphewas.com).