← Back to cohort
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Rebecca Sims, Sven J. van der Lee, Adam C. Naj, Céline Bellenguez, Nandini Badarinarayan, Jóhanna Jakobsdóttir, Brian W. Kunkle, Anne Boland, Rachel Raybould, Eden R. Martin, Benjamin Grenier‐Boley, Stefanie Heilmann‐Heimbach, Vincent Chouraki, Amanda Kuzma, Kristel Sleegers, Maria Vronskaya, Agustı́n Ruiz, Robert Graham, Robert Olaso, Per Hoffmann, Megan L. Grove, Badri N. Vardarajan, Mikko Hiltunen, Markus M. Nöthen, Charles C. White, Kara L. Hamilton‐Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W. Beecham, Cécile Dulary, Stefan Herms, Albert V. Smith, Cory C. Funk, Céline Derbois, Andreas J. Forstner, Shahzad Ahmad, Hong‐Dong Li, Delphine Bacq, Denise Harold, Claudia L. Satizábal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A. Brody, Liming Qu, Pascual Sánchez‐Juan, Taniesha Morgan, Frank J. Wolters, Yi Zhao, Florentino Sánchez-García, Nicola Denning, Myriam Fornage, John Malamon, María Cándida Déniz Naranjo, Elisa Majounie, Thomas H. Mosley, Beth A. Dombroski, David Wallon, Michelle K. Lupton, Josée Dupuis, Patrice L. Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B. Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno–Grau, Jeremy D. Burgess, Vincenzo Solfrizzi, Hieab H.H. Adams, Mariet Allen, Davide Seripa, Pau Pástor, L. Adrienne Cupples, Nathan D. Price, Didier Hannequin, Ana Frank, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E. Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K. Crane, Florence Pasquier, Virginia Boccardi, Isabel Henández, Robert C. Barber, Martin Scherer, Lluís Tárraga, Perrie M. Adams, Markus Leber, Yuning Chen, Marilyn S. Albert, Steffi G. Riedel‐Heller, Valur Emilsson, Duane Beekly, Anne Braae, Reinhold Schmidt, Deborah Blacker, Carlo Masullo, Helena Schmidt, Rachelle S. Doody, Gianfranco Spalletta, W. T. Longstreth, Thomas Fairchild, Paola Bossù, Oscar L. López, Matthew P. Frosch, Eleonora Sacchinelli, Bernardino Ghetti, Qiong Yang, Ryan Huebinger, Frank Jessen, Shuo Li, M. Ilyas Kamboh, John C. Morris, Óscar Sotolongo‐Grau, Mindy J. Katz, Chris Corcoran, Melanie Dunstan, Amy Braddel, Charlene Thomas, Alun Meggy, Iain Marshall, Amy Gerrish, Jade Chapman, Miquel Aguilar, Sarah Taylor, Matt Hill, Mónica Díez-Fairén, Angela Hodges, Bruno Vellas, Hilkka Soininen, Iwona Kłoszewska, Makrina Daniilidou, James Uphill, Yogen Patel, Joseph T. Hughes, Jenny Lord, James Turton, Annette M. Hartmann, Roberta Cecchetti, Chiara Fenoglio, María Serpente, Marina Arcaro, Carlo Caltagirone, Maria Donata Orfei, Antonio Ciaramella, Sabrina Pichler, Manuel Mayhaus, Wei Gu, Alberto Lleó, Juan Fortea, Rafael Blesa, Imelda Barber, Keeley J. Brookes, Chiara Cupidi, Raffaele Maletta, David Carrell, Sandro Sorbi, Susanne Moebus, Maria Urbano, Alberto Pilotto, Johannes Kornhuber, Paolo Bosco, Stephen Todd, David Craig, Janet Johnston, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Nick C. Fox, John Hardy, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Clinton T. Baldwin, Lisa L. Barnes, Sandra Barral, Thomas G. Beach, James T. Becker, Eileen H. Bigio, Thomas D. Bird, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Jeffrey M. Burns, Joseph D. Buxbaum, Nigel J. Cairns, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Carolina Ceballos Diaz, Helena C. Chui, David G. Clark, David H. Cribbs, Elizabeth Crocco, Charles DeCarli, Malcolm Dick, Ranjan Duara, Denis A. Evans, Kelley M. Faber, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Steven H. Ferris, Tatiana M. Foroud, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, John R. Gilbert, Caroline Graff, Robert C. Green, John H. Growdon, Ronald L. Hamilton, Lindy E. Harrell, Lawrence S. Honig, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Erin L. Abner, Lee‐Way Jin, Gyungah Jun, Anna Karydas, Ronald Kim, Neil W. Kowall, Joel H. Kramer, Frank M. LaFerla, James J. Lah, James B. Leverenz, Allan I. Levey, Ge Li, Andrew P. Lieberman, Kathryn L. Lunetta, Constantine G. Lyketsos, Daniel Marson, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew McDavid, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, Jill R. Murrell, Amanda Myers, Sid E. O’Bryant, John Olichney, V. Shane Pankratz, Joseph E. Parisi, Henry L. Paulson, William Perry, Elaine R. Peskind, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, Barry Reisberg, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Mark A. Sager, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Russell H. Swerdlow, Rudolph E. Tanzi, Tricia A. Thornton‐Wells, John Q. Trojanowski, Juan C. Troncoso, Vivianna M. Van Deerlin, Linda J. Van Eldik, Harry V. Vinters, Jean Paul Vonsattel, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Randall L. Woltjer, Clinton B. Wright, Chang‐En Yu, Lei Yu, Fabienne Garzia, Feroze Golamaully, Gislain Septier, Sebastien Engelborghs, Rik Vandenberghe, Peter Paul De Deyn, Carmen Muñoz Fernadez, Håkan Thonberg, Charlotte Forsell, Lena Lilius, Anne Kinhult‐Ståhlbom, Lena Kilander, RoseMarie Brundin, Letizia Concari, Seppo Helisalmi, Anne M. Koivisto, Annakaisa Haapasalo, Vincent Dermecourt, Nathalie Fiévet, Olivier Hanon, Carole Dufouil, Alexis Brice, Karen Ritchie, Bruno Dubois, J.J. Himali, C. Dirk Keene, JoAnn T. Tschanz, Annette L. Fitzpatrick, Walter A. Kukull, Maria C. Norton, Thor Aspelund, Eric B. Larson, Ron Munger, Jerome I. Rotter, Richard B. Lipton, María J. Bullido, Albert Hofman, Thomas J. Montine, Eliécer Coto, Eric Boerwinkle, Ronald C. Petersen, Victoria Álvarez, Fernando Rivadeneira, Eric M. Reiman, Maura Gallo, Christopher J. O’Donnell, Joan Reisch, Amalia C. Bruni, Donald R. Royall, Martin Dichgans, Mary Sano, Daniela Galimberti, Peter St George‐Hyslop, Elio Scarpini, Debby W. Tsuang, Michelangelo Mancuso, Ubaldo Bonuccelli, Ashley R. Winslow, Antonio Daniele, Chuang‐Kuo Wu, Oliver Peters, Benedetta Nacmias, Reinhard Heun, Carol Brayne, David C. Rubinsztein, José Brás, Rita Guerreiro, Ammar Al‐Chalabi, Christopher E. Shaw, John Collinge, David Mann, Magda Tsolaki, Jordi Clarimón, Rebecca Sussams, Simon Lovestone, Michael O‘Donovan, Michael J. Owen, Timothy W. Behrens, Simon Mead, Alison Goate, André G. Uitterlinden, Clive Holmes, Carlos Cruchaga, Martin Ingelsson, David A. Bennett, John Powell, Todd E. Golde, Philip L. De Jager, Kevin Morgan, Nilüfer Ertekin‐Taner, Onofre Combarros, Bruce M. Psaty, Peter Passmore, Steven G. Younkin, Claudine Berr, Vilmundur Guðnason, Dan Rujescu, Dennis W. Dickson, Jean‐François Dartigues, Anita L. DeStefano, Sara Ortega‐Cubero, Håkon Håkonarson, Dominique Campion, Merçé Boada, John Kauwe, Lindsay A. Farrer, Christine Van Broeckhoven, M. Arfan Ikram, Lesley Jones, Jonathan L. Haines, Christophe Tzourio, Lenore J. Launer, Valentina Escott‐Price, Richard Mayeux, Jean‐François Deleuze, Najaf Amin, Peter Holmans, Margaret A Pericak‐Vance, Philippe Amouyel, Cornelia M. van Duijn, Alfredo Ramı́rez, Li‐San Wang, Jean‐Charles Lambert, Sudha Seshadri, Julie Williams, Gerard D. Schellenberg
Bibliographic record
VenueNature Genetics · 2017
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute on Deafness and Other Communication DisordersNational Eye InstituteNational Human Genome Research InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Cancer InstituteEuropean Regional Development FundBijzonder Onderzoeksfonds UGentInstituto de Salud Carlos IIIMenzies Centre for Australian Studies, King's College London, University of LondonSixth Framework ProgrammeUniversity of California, IrvineUniversity of California, San FranciscoUniversity of California, San DiegoUniversity of California, DavisUniversity of California, Los AngelesGenentechNational Institutes of HealthVetenskapsrådetArizona Biomedical Research CommissionFundación Ramón ArecesUK Dementia Research InstituteInstituut Born-BungeIXICOHjartaverndBiogenMarcus och Amalia Wallenbergs minnesfondGeneralitat de CatalunyaUniversitat Autònoma de BarcelonaMinisterio de Economía y CompetitividadErasmus Medisch CentrumUniversity College London Hospitals NHS Foundation TrustMutuelle Générale de l'Education NationaleAcademy of FinlandServierSwedish Brain PowerNederlandse Organisatie voor Wetenschappelijk OnderzoekNorth Bristol NHS TrustUniversiteit AntwerpenUniversidad Autónoma de MadridKuopion Yliopistollinen SairaalaKarolinska InstitutetFonds Wetenschappelijk OnderzoekSouth London and Maudsley NHS Foundation TrustBelgian Federal Science Policy OfficeNational Center for Advancing Translational SciencesBundesministerium für Bildung und ForschungAXA Research FundMinistero della SaluteH. Lundbeck A/SInstitut National de la Santé et de la Recherche MédicaleDeutsche ForschungsgemeinschaftCardiff UniversityUniversity of NottinghamBrigham Young UniversityFondation pour la Recherche sur AlzheimerCanadian Institutes of Health ResearchEuropean CommissionBioClinicaNewcastle UniversityUniversitat de BarcelonaKing's College LondonOffice of Research and DevelopmentParkinson's UKVlaamse regeringNational Institute for Health and Care ResearchStichting MS ResearchUniversity of SouthamptonAlzheimer's SocietyCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasAgence Nationale de la RechercheWellcome TrustArizona Department of Health ServicesJohns Hopkins UniversityDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseCurePSPNorthern California Institute for Research and EducationUniversität des SaarlandesRush UniversityCentro de Biología Molecular Severo OchoaMotor Neurone Disease AssociationNovartis Pharmaceuticals CorporationZonMwUniversity of CambridgeStockholms Läns LandstingUniversity of PittsburghPfizerEU Joint Programme – Neurodegenerative Disease ResearchUniversity of WashingtonBrightFocus FoundationFondazione Cassa di Risparmio di Pistoia e PesciaAlzheimer's AssociationNorthwestern UniversityMedical Research CouncilMayo Foundation for Medical Education and ResearchEmory UniversityUniversidad de NavarraU.S. Department of Veterans AffairsFondation de FranceUniversity of PennsylvaniaSanofiEisaiUniversity of Southern CaliforniaU.S. Department of DefenseHersenstichtingEli Lilly and CompanyYork UniversityVanderbilt UniversityGlaxoSmithKlineMayo ClinicQueen's UniversityUniversity of MiamiMassachusetts General HospitalAgence Française de Sécurité Sanitaire des Produits de SantéMeso Scale DiagnosticsFondation pour la Recherche MédicaleBristol-Myers Squibb
KeywordsTREM2Nonsynonymous substitutionBiologyMinor allele frequencyGeneticsGenome-wide association studyMicrogliaAlzheimer's diseaseGenotypingAlleleGeneGenotypeAllele frequencyDiseaseSingle-nucleotide polymorphismImmunologyGenomeImmune systemMedicineInternal medicine
Abstract
No abstract in any covered source. Its absence is recorded, not treated as a negative.
No abstract. This is not a gap in this database; OpenAlex has none either. 23.3% of the frame is in this state, and the screen finds HALF as much metaresearch here, so the absence is a measured bias rather than a missing field.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.035
GPT teacher head0.295
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations1,104
Published2017
Admission routes2
Has abstractno