{"id":"W4412728341","doi":"10.1101/2025.07.28.25332293","title":"Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation","year":2025,"lang":"en","type":"preprint","venue":"medRxiv","topic":"Genetic Associations and Epidemiology","field":"Biochemistry, Genetics and Molecular Biology","cited_by":1,"is_retracted":false,"has_abstract":true,"ca_institutions":"Ontario Brain Institute; University of Toronto; University Health Network","funders":"National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; ZonMw; Fundação para a Ciência e a Tecnologia; National Health and Medical Research Council; Fondation pour la Recherche sur Alzheimer; Universität Heidelberg; Ludwig Boltzmann Gesellschaft; Vetenskapsrådet; Eisai; Ministerio de Economía y Competitividad; Sorbonne Université; Generalitat de Catalunya; European Regional Development Fund; Bundesministerium für Bildung und Forschung; National Institutes of Health; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; Sahlgrenska Universitetssjukhuset; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; Agence Nationale de la Recherche; Instituto de Salud Carlos III; National Research Foundation; EU Joint Programme – Neurodegenerative Disease Research; Medical Research Council; Universidade de Aveiro; AXA Research Fund; Alzheimer's Association","keywords":"Disease; Polygenic risk score; Hazard ratio; Demography; Psychology; Medicine; Internal medicine; Biology; Genetics; Confidence interval; Gene","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0171978,0.0009061422,0.0007496254,0.001659023,0.0002842696,0.0008352181,0.001194317,0.0006903188,0.001625121],"category_scores_gemma":[0.02005446,0.0003116377,0.001492406,0.001088722,0.0003950188,0.0006636885,0.001381181,0.001121772,0.000392124],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0005767311,"about_ca_system_score_gemma":0.001204787,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.01199547,"about_ca_topic_score_gemma":0.00599062,"domain_scores_codex":[0.9970504,0.00208497,0.0001287132,0.0004305312,0.0002053214,0.0001001334],"domain_scores_gemma":[0.9899456,0.007456498,0.0005658618,0.0008320137,0.0009052571,0.0002947294],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.001736182,0.0005616182,0.5409746,0.0001474899,0.002226487,0.0003216049,0.0002470668,0.3264254,0.0007358912,0.003457881,0.004425764,0.1187401],"study_design_scores_gemma":[0.0001437445,0.000248102,0.04516991,0.00003471953,0.0001671229,0.0001064591,0.00004460951,0.9505422,0.0002862291,0.002523518,0.0007048778,0.00002853342],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.8479307,0.0007736736,0.144656,0.0006762061,0.00008457701,0.000259912,0.003640364,0.0004813897,0.00149717],"genre_scores_gemma":[0.9521347,0.0002698716,0.04352624,0.0001180305,0.0000494263,0.0001781382,0.003071752,0.0000432487,0.0006085823],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0171978,"threshold_uncertainty_score":0.09095174,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.05248202968223536,"score_gpt":0.3055493728441128,"score_spread":0.2530673431618774,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}