{"id":"W4412679067","doi":"10.1101/2025.07.27.25332260","title":"Analysis of whole genome sequence data shows association of Alzheimer’s disease with rare coding variants in <i>ABCA7, PSEN1, SORL1</i> and <i>TREM2</i>","year":2025,"lang":"en","type":"preprint","venue":"medRxiv","topic":"Alzheimer's disease research and treatments","field":"Medicine","cited_by":2,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"National Institute on Minority Health and Health Disparities; National Human Genome Research Institute; National Institute on Aging; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis; Canadian Institutes of Health Research; Genentech; IXICO; H. Lundbeck A/S; Servier; Eisai; National Institutes of Health; Ministry of Science, ICT and Future Planning; Hope Center for Neurological Disorders; University of Southern California; University College London; Northern California Institute for Research and Education; University of Pennsylvania; Pfizer; BioClinica; Biogen; U.S. Department of Defense; Eli Lilly and Company; Bristol-Myers Squibb; Meso Scale Diagnostics; Alzheimer's Disease Neuroimaging Initiative; National Heart, Lung, and Blood Institute; Novartis Pharmaceuticals Corporation; Alzheimer's Association","keywords":"Nonsynonymous substitution; PSEN1; Biology; Genetics; Genome-wide association study; Genetic association; Gene; TREM2; Disease; Coding region; Alzheimer's disease; Single-nucleotide polymorphism; Genome; Medicine; Genotype; Presenilin; Pathology","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004360471,0.0001629421,0.00025814,0.0008065323,0.0002532428,0.0003348987,0.000113314,0.0002798636,0.00151384],"category_scores_gemma":[0.001031456,0.0001053144,0.0004165787,0.0007731992,0.0002299229,0.0001053654,0.0001932861,0.0002767245,0.0002224342],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001185234,"about_ca_system_score_gemma":0.000103137,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001294467,"about_ca_topic_score_gemma":0.002719561,"domain_scores_codex":[0.9996874,0.00007487704,0.00003297732,0.0001058279,0.00006190747,0.00003704318],"domain_scores_gemma":[0.9991491,0.0004392452,0.0002009772,0.0000615384,0.0000699044,0.00007924024],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.002508028,0.0001397818,0.5421282,0.0002319639,0.0008800187,0.002460366,0.0003643355,0.0007478482,0.435659,0.0001254582,0.0006194292,0.0141356],"study_design_scores_gemma":[0.0000199409,0.0001622202,0.990026,0.000006995435,0.0001173263,0.001541792,0.000095602,0.0008809633,0.006584147,0.00004890282,0.0005094858,0.000006706645],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.998801,0.00009442362,0.000359655,0.00002415642,0.000002836689,0.000003762478,0.00058782,0.000006831001,0.0001194453],"genre_scores_gemma":[0.996568,0.00009134551,0.001069938,0.00003267481,0.000005588648,0.000007598146,0.002006914,0.000006721712,0.0002113613],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.00151384,"threshold_uncertainty_score":0.005064309,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.06806364299318364,"score_gpt":0.3391719729337001,"score_spread":0.2711083299405165,"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."}}