{"id":"W4414912953","doi":"10.1016/j.cell.2025.09.012","title":"Genetic modifiers and ascertainment drive variable expressivity of complex disorders","year":2025,"lang":"en","type":"article","venue":"Cell","topic":"Genomics and Rare Diseases","field":"Biochemistry, Genetics and Molecular Biology","cited_by":10,"is_retracted":false,"has_abstract":true,"ca_institutions":"McMaster University","funders":"National Institute of Neurological Disorders and Stroke; U.S. National Library of Medicine; National Institute of General Medical Sciences","keywords":"Expressivity; Context (archaeology); Proband; Disease; Phenotype; Gene; Population; Penetrance","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":[0.002114588,0.0003352258,0.0005343999,0.001202087,0.0003616873,0.000860468,0.0004719644,0.0003741453,0.001300745],"category_scores_gemma":[0.01089682,0.0002430618,0.000396176,0.00112945,0.0007437557,0.0004214075,0.001010631,0.0006743913,0.0001110871],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002305898,"about_ca_system_score_gemma":0.0001758244,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.002472888,"about_ca_topic_score_gemma":0.003013723,"domain_scores_codex":[0.9975106,0.0009452803,0.0001719132,0.000842573,0.0003606889,0.0001689495],"domain_scores_gemma":[0.9916853,0.004644775,0.001948217,0.001290001,0.0001982427,0.0002335362],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.0003994386,0.00002069984,0.9739056,0.00002578132,0.000419239,0.0006824138,0.0004560467,0.0006669519,0.01391013,0.0005283145,0.00009265707,0.008892785],"study_design_scores_gemma":[0.000009052276,0.00003954452,0.9954017,0.00000987247,0.0001573393,0.0008894283,0.00008609078,0.0009215332,0.001557568,0.0006935771,0.0002244636,0.000009712971],"study_design_candidate":"bench_or_experimental","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9974768,0.0003797584,0.001395607,0.00006089211,0.000004272241,0.000006494081,0.0002351597,0.000008406707,0.0004326985],"genre_scores_gemma":[0.9993101,0.0001052651,0.0003888394,0.0000148055,0.00000700993,0.000003662386,0.0001020537,0.000006991243,0.00006125034],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002472888,"threshold_uncertainty_score":0.0111832,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.00408131857436286,"score_gpt":0.2104152088393511,"score_spread":0.2063338902649882,"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."}}