{"id":"W2592518050","doi":"10.1038/ng.3916","title":"Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease","year":2017,"lang":"en","type":"article","venue":"Nature Genetics","topic":"Neuroinflammation and Neurodegeneration Mechanisms","field":"Neuroscience","cited_by":1104,"is_retracted":false,"has_abstract":false,"ca_institutions":"Occupational Cancer Research Centre; University of Toronto","funders":"National Center for Research Resources; National Institute of Neurological Disorders and Stroke; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Deafness and Other Communication Disorders; National Eye Institute; National Human Genome Research Institute; National Institute of Mental Health; National Heart, Lung, and Blood Institute; National Institute on Aging; National Cancer Institute; European Regional Development Fund; Bijzonder Onderzoeksfonds UGent; Instituto de Salud Carlos III; Menzies Centre for Australian Studies, King's College London, University of London; Sixth Framework Programme; University of California, Irvine; University of California, San Francisco; University of California, San Diego; University of California, Davis; University of California, Los Angeles; Genentech; National Institutes of Health; Vetenskapsrådet; Arizona Biomedical Research Commission; Fundación Ramón Areces; UK Dementia Research Institute; Instituut Born-Bunge; IXICO; Hjartavernd; Biogen; Marcus och Amalia Wallenbergs minnesfond; Generalitat de Catalunya; Universitat Autònoma de Barcelona; Ministerio de Economía y Competitividad; Erasmus Medisch Centrum; University College London Hospitals NHS Foundation Trust; Mutuelle Générale de l'Education Nationale; Academy of Finland; Servier; Swedish Brain Power; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; North Bristol NHS Trust; Universiteit Antwerpen; Universidad Autónoma de Madrid; Kuopion Yliopistollinen Sairaala; Karolinska Institutet; Fonds Wetenschappelijk Onderzoek; South London and Maudsley NHS Foundation Trust; Belgian Federal Science Policy Office; National Center for Advancing Translational Sciences; Bundesministerium für Bildung und Forschung; AXA Research Fund; Ministero della Salute; H. Lundbeck A/S; Institut National de la Santé et de la Recherche Médicale; Deutsche Forschungsgemeinschaft; Cardiff University; University of Nottingham; Brigham Young University; Fondation pour la Recherche sur Alzheimer; Canadian Institutes of Health Research; European Commission; BioClinica; Newcastle University; Universitat de Barcelona; King's College London; Office of Research and Development; Parkinson's UK; Vlaamse regering; National Institute for Health and Care Research; Stichting MS Research; University of Southampton; Alzheimer's Society; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas; Agence Nationale de la Recherche; Wellcome Trust; Arizona Department of Health Services; Johns Hopkins University; Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease; CurePSP; Northern California Institute for Research and Education; Universität des Saarlandes; Rush University; Centro de Biología Molecular Severo Ochoa; Motor Neurone Disease Association; Novartis Pharmaceuticals Corporation; ZonMw; University of Cambridge; Stockholms Läns Landsting; University of Pittsburgh; Pfizer; EU Joint Programme – Neurodegenerative Disease Research; University of Washington; BrightFocus Foundation; Fondazione Cassa di Risparmio di Pistoia e Pescia; Alzheimer's Association; Northwestern University; Medical Research Council; Mayo Foundation for Medical Education and Research; Emory University; Universidad de Navarra; U.S. Department of Veterans Affairs; Fondation de France; University of Pennsylvania; Sanofi; Eisai; University of Southern California; U.S. Department of Defense; Hersenstichting; Eli Lilly and Company; York University; Vanderbilt University; GlaxoSmithKline; Mayo Clinic; Queen's University; University of Miami; Massachusetts General Hospital; Agence Française de Sécurité Sanitaire des Produits de Santé; Meso Scale Diagnostics; Fondation pour la Recherche Médicale; Bristol-Myers Squibb","keywords":"TREM2; Nonsynonymous substitution; Biology; Minor allele frequency; Genetics; Genome-wide association study; Microglia; Alzheimer's disease; Genotyping; Allele; Gene; Genotype; Allele frequency; Disease; Single-nucleotide polymorphism; Immunology; Genome; Immune system; Medicine; Internal medicine","routes":{"ca_aff":true,"ca_fund":true,"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":[0.0003745204,0.0008917582,0.0003377074,0.0009136017,0.00071678,0.0005067646,0.0004218386,0.001195404,0.003727905],"category_scores_gemma":[0.0009100821,0.0002040747,0.0005264821,0.0006717066,0.0006182793,0.0003194313,0.0004546707,0.0006862921,0.0004679113],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00024929,"about_ca_system_score_gemma":0.0002243248,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.001781537,"about_ca_topic_score_gemma":0.002669443,"domain_scores_codex":[0.9996926,0.00006983725,0.00005051614,0.00006721994,0.00008005757,0.0000397605],"domain_scores_gemma":[0.9994407,0.0002152425,0.000185364,0.0000494458,0.00004074673,0.00006837714],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"observational","study_design_scores_codex":[0.005183122,0.0003073024,0.1789807,0.0002818336,0.0008288457,0.08871207,0.001503258,0.001705152,0.6767278,0.0100643,0.003167509,0.03253803],"study_design_scores_gemma":[0.0007574471,0.0007135624,0.6552594,0.0003700531,0.001950979,0.1997907,0.001414712,0.008976582,0.0940012,0.022445,0.01411287,0.000207585],"study_design_candidate":"observational","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9932327,0.0006270171,0.002968587,0.0003867401,0.00005372507,0.00001853886,0.0006168127,0.0001192863,0.001976605],"genre_scores_gemma":[0.9977965,0.0001370185,0.001225122,0.00009838551,0.00005224229,0.000008278867,0.0001762147,0.0000259506,0.0004802977],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003727905,"threshold_uncertainty_score":0.01247114,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.03495807231275978,"score_gpt":0.2946570760368707,"score_spread":0.2596990037241109,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). 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