{"id":"W4411661442","doi":"10.1002/alz.70377","title":"Novel early‐onset Alzheimer‐associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways","year":2025,"lang":"en","type":"article","venue":"Alzheimer s & Dementia","topic":"Genetic Associations and Epidemiology","field":"Biochemistry, Genetics and Molecular Biology","cited_by":7,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"National Institute on Minority Health and Health Disparities; National Center for Research Resources; National Institute of Neurological Disorders and Stroke; National Cancer Institute; National Institute of Biomedical Imaging and Bioengineering; National Human Genome Research Institute; National Institute of Mental Health; National Institute on Aging; University of California, Irvine; University of California, Davis; IXICO; BrightFocus Foundation; Hersenstichting; North Bristol NHS Trust; Medical Research Council; Boston University; Servier; Stichting MS Research; U.S. Department of Defense; University of Alabama at Birmingham; BRACE; Northern California Institute for Research and Education; GE Healthcare; Universitat de Barcelona; Rush University; Takeda Pharmaceutical Company; University of Pittsburgh; University of Arizona; Nederlandse Hersenbank; McDonnell Center for Systems Neuroscience; University of California, San Diego; Johns Hopkins University; University of California, Los Angeles; University of Washington; York University; University of Miami; Northwestern University; U.S. Department of Veterans Affairs; University of Pennsylvania; Indiana University; Vanderbilt University; Hope Center for Neurological Disorders; Wellcome Trust; Eisai; University of Southern California; Duke University; Michael J. Fox Foundation for Parkinson's Research; Emory University; AbbVie; Columbia University; Massachusetts General Hospital; National Institutes of Health; Alzheimer's Drug Discovery Foundation; Office of Research and Development; Alzheimer's Association; Newcastle University; University of Kentucky; New York University; Alzheimer's Research Trust; Oregon Health and Science University; University of Michigan; University of California, San Francisco; Mayo Clinic; Howard Hughes Medical Institute; Chan Zuckerberg Initiative","keywords":"Genome-wide association study; Biology; Expression quantitative trait loci; Gene; Quantitative trait locus; Genetics; Genetic association; Disease; Candidate gene; TREM2; Immune dysregulation; Single-nucleotide polymorphism; Medicine; Immune system; Genotype; Internal medicine","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":[0.0007280897,0.0008776489,0.0006021122,0.0009268294,0.000357823,0.000708884,0.000368816,0.0003972371,0.001998964],"category_scores_gemma":[0.001351424,0.0001922498,0.000839324,0.001205641,0.0003760103,0.0002312905,0.0004720935,0.0003672255,0.0002157154],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002135643,"about_ca_system_score_gemma":0.0003471641,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0018784,"about_ca_topic_score_gemma":0.002140401,"domain_scores_codex":[0.9994786,0.0001316203,0.00005039122,0.0002047283,0.00007945158,0.0000551485],"domain_scores_gemma":[0.9992002,0.0003052055,0.000287434,0.00007014063,0.00007476058,0.00006232537],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.002434238,0.0001551731,0.8555462,0.0004521632,0.002001575,0.003156269,0.0004480924,0.001230703,0.1024645,0.000653516,0.000538926,0.03091866],"study_design_scores_gemma":[0.00008079185,0.0001959108,0.9832478,0.00006221453,0.0014018,0.002016325,0.0001389002,0.001954336,0.008238592,0.001280365,0.001356512,0.00002647337],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9941089,0.001890745,0.002423948,0.0001070548,0.00001541362,0.00001686001,0.0008729751,0.00004287789,0.0005213568],"genre_scores_gemma":[0.9959656,0.0006417381,0.00250908,0.00008278312,0.00001889851,0.00001699242,0.0004410906,0.00001710444,0.00030664],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001998964,"threshold_uncertainty_score":0.006687164,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01663868865682146,"score_gpt":0.2512521983662543,"score_spread":0.2346135097094329,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). 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