{"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":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.00002502148,0.00006910175,0.000078502,0.00001820495,0.00004009857,0.000007008163,0.00007736841,0.00004611299,0.00001524121],"category_scores_gemma":[0.000007955799,0.00006657786,0.00003263781,0.00002969898,0.00006530168,6.301678e-7,0.00009306976,0.00002009524,6.024902e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000004155045,"about_ca_system_score_gemma":0.00004175353,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00003645895,"about_ca_topic_score_gemma":0.000006274387,"domain_scores_codex":[0.999594,0.00001771874,0.00008668619,0.0001687484,0.00003354641,0.00009934267],"domain_scores_gemma":[0.9997309,0.000006316813,0.00003253506,0.0001722442,0.00001961002,0.00003838309],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.00003357281,0.0001137593,0.004896322,0.00008535965,0.00003652177,6.795979e-7,0.00003484305,0.0008047246,0.9897999,0.0001433208,0.002977899,0.001073143],"study_design_scores_gemma":[0.003277791,0.0004412597,0.1662183,0.0000544673,0.000202086,0.000002971002,0.0008873458,0.003139515,0.6444517,0.005559295,0.1750752,0.000690154],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9865903,0.001345865,0.003121881,0.00003316706,0.00005269368,0.0001135335,0.0000277631,0.00000259329,0.008712172],"genre_scores_gemma":[0.9976952,0.0003510099,0.001094014,0.0001053285,0.00001266864,0.00000816089,0.00003064945,0.000005162515,0.0006977785],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.3453482,"threshold_uncertainty_score":0.2714967,"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."}}