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A novel Alzheimer disease locus located near the gene encoding tau protein
Gyungah Jun, Carla A. Ibrahim‐Verbaas, Maria Vronskaya, Jaeyoon Chung, Adam C. Naj, Brian W. Kunkle, Li‐Shun Wang, Joshua C. Bis, Céline Bellenguez, Denise Harold, Kathryn L. Lunetta, Anita L. DeStefano, Benjamin Grenier‐Boley, Rebecca Sims, Gary W. Beecham, Albert V. Smith, Vincent Chouraki, Kara L. Hamilton‐Nelson, M. Arfan Ikram, Nathalie Fiévet, Nicola Denning, Eden R. Martin, Helena Schmidt, Melanie Dunstan, Otto Valladares, Agustín Ruiz Laza, Diana Zélénika, Alfredo Ramı́rez, Tatiana Foroud, Anne Boland, Tim Becker, Walter A. Kukull, Sven J. van der Lee, Florence Pasquier, Carlos Cruchaga, Duane Beekly, Annette L. Fitzpatrick, Olivier Hanon, Michael Gill, Robert C. Barber, Vilmundur Guðnason, Dominique Campion, Seth Love, David A. Bennett, Najaf Amin, Claudine Berr, Magda Tsolaki, Joseph D. Buxbaum, Oscar L. López, Vincent Deramecourt, Nick C. Fox, Laura B. Cantwell, Lluís Tárraga, Carole Dufouil, John Hardy, Paul K. Crane, Gudny Eiriksdottir, Didier Hannequin, Robert Clarke, Denis A. Evans, Thomas H. Mosley, Luc Letenneur, Carol Brayne, Wolfgang Maier, Philip L. De Jager, Valur Emilsson, Dartigues Jf, Harald Hampel, M. Ilyas Kamboh, Renée F.A.G. de Bruijn, Christophe Tzourio, Pau Pástor, Eric B. Larson, Jerome I. Rotter, Michael O‘Donovan, Thomas J. Montine, Michael A. Nalls, Simon Mead, Eric M. Reiman, Pálmi V. Jónsson, Clive Holmes, Peter St George‐Hyslop, Merçé Boada, Peter Passmore, Jens R. Wendland, R. Schmidt, Kevin Morgan, Ashley R. Winslow, John Powell, M Carasquillo, Steven G. Younkin, Jóhanna Jakobsdóttir, John Kauwe, Dan Rujescu, Markus M. Nöthen, Albert Hofman, Lesley Jones, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Clinton T. Baldwin, Michjael M Barmada, Lisa L. Barnes, Thomas G. Beach, James T. Becker, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Nigel J. Cairns, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason J. Corneveaux, David H. Cribbs, Elizabeth Crocco, Charles DeCarli, Steven T. DeKosky, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Nilüfer Ertekin‐Taner, Kelley M. Faber, Thomas Fairchild, Kenneth B. Fallon, Martin R. Farlow, Steven H. Ferris, Matthew P. Frosch, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Jonathan D. Glass, Caroline Graff, Robert C. Green, John H. Growdon, Håkon Håkonarson, Ronald L. Hamilton, Lindy E. Harrell, Elizabeth Head, Lawrence S. Honig, Ryan Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee‐Way Jin, Anna Karydas, John SK Kauwe, Ronald Kim, Edward H. Koo, Neil W. Kowall, Joel H. Kramer, Frank M. LaFerla, James J. Lah, James B. Leverenz, Allan I. Levey, Li Ge, Andrew P. Lieberman, Chiao‐Feng Lin, Constantine G. Lyketsos, Wendy J. Mack, 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, John C. Morris, Shubhabrata Mukherjee, Jill R. Murrell, Amanda Myers, Sid E. O’Bryant, John Olichney, V. Shane Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine R. Peskind, Ronald Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, Barry Reisberg, Joan Reisch, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Rudolph E. Tanzi, Tricia A. Thornton‐Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Jean Paul Vonsattel, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang‐Kuo Wu, Chang-En Yu, Lei Yu, Rhoda Au, Philip A. Wolf, Alexa Beiser, Claudia L. Satizábal, André G. Uitterlinden, Fernando Rivadeneira, Peter J. Koudstaal, W.T. Longstreth, Lewis H. Kuller, Thomas Lumley, Kenneth Rice, Tamara B Harris, Michael A. Nalls, Josef Marksteiner, Peter Dal‐Bianco, Anna Maria Töglhofer, Paul Freudenberger, Gerhard Ransmayr, Thomas Benke, Anna M. Toeglhofer, Eric Boerwinkle, Jan Bressler, Myriam Fornage, Francisco Jesús Morón, Isabel Hernández, Maiteé Rosende Roca, Ana Mauleón, Montserrat Alegret, Reposo Ramírez‐Lorca, Antonio González-Perez, Annick Alpérovitch, Victoria Álvarez, Pascale Barberger‐Gateau, Karolien Bettens, Paola Bossù, Alexis Brice, María J. Bullido, P Caffara, Jordi Clarimón, Onofre Combarros, Eliécer Coto, Maria del Zampo, Marc Délepine, María Cándida Déniz Naranjo, Jacques Epelbaum, Laura Fratiglioni, Daniela Galimberti, Mikko Hiltunen, Martin Ingelsson, Lina Keller, Lars Lannfelt, Alberto Lleó, Michelangelo Mancuso, Ignacio Mateo, Patrizia Mecocci, Benedetta Nacmias, Francesco Panza, Alberto Pilotto, Florentino Sánchez-García, Elio Scarpini, Davide Seripa, Kristel Sleegers, Hlikka Soininen, Sandro Sorbi, Gianfranco Spalletta, David Wallon, Charlene Thomas, Amy Gerrish, Jade Chapman, Alexandra Stretton, Angharad R. Morgan, Harriet G. Oldham, Michael J. Owen, Patrick G. Kehoe, Christopher Medway, Kristelle Brown, Jenny Lord, James Turton, Nigel M. Hooper, Emma Vardy, Jason D. Warren, Jonathan M. Schott, James Uphill, Paul Hollingworth, DClin Psy, Natalie S. Ryan, Martin N. Rossor, John Collinge, Yoav Ben‐Shlomo, Makrina Daniilidou, Olymbia Gkatzima, Michelle K. Lupton, Maria Koutroumani, Despoina Avramidou, Antonia Germanou, Frank Jessen, Steffi G. Riedel‐Heller, Martin Dichgans, Reiner Heun, Heike Kölsch, Britta Schürmann, Christine Herold, André Lacour, Dmitriy Drichel, Per Hoffmann, Johannes Kornhuber, Wei Gu, Thomas Feulner, Manuel Mayhaus, Sabrina Pichler, Hendrik van den Bussche, Brian Lawlor, Aoibhinn Lynch, David Mann, A. David Smith, Donald Warden, Gordon Wilcock, Isabella Heuser, Jens Wiltfang, Lutz Frölich, Michael Hüll, Kevin H. Mayo, Gill Livingston, Nicholas Bass, Hugh Gurling, Andrew McQuillin, Rhian Gwilliam, Ammar Al‐Chalabi, Christopher E. Shaw, Andrew B. Singleton, Rita Guerreiro, Giancarlo Russo, Karl‐Heinz Jöckel, Susanne Moebus, Norman Klopp, H‐Erich Wichmann, Li Ma, Gina Bisceglio, Elizabeth Fisher, Stuart Pickering‐Brown, David Craig, Janet Johnston, Bernadette McGuinness, Stephen Todd, David C. Rubinsztein, Simon Lovestone, John Gallacher, Petroula Proitsi, Sara Ortega‐Cubero, Jonathan L. Haines, Bruce M. Psaty, Christine Van Broeckhoven, Peter Holmans, L J Launer, Richard Mayeux, M Lathrop, Alison Goate, Valentina Escott‐Price, Sudha Seshadri, Margaret A Pericak‐Vance, Philippe Amouyel, Julie Williams, Cornelia M. van Duijn, Gerard D. Schellenberg, Lindsay A. Farrer
Bibliographic record
VenueMolecular Psychiatry · 2015
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOccupational Cancer Research CentreMcGill University and Génome Québec Innovation CentreUniversity of Toronto
FundersNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesAlzheimer's Research TrustNational Cancer InstituteNational Institute of Biomedical Imaging and BioengineeringNational Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingSynarcInstituto de Salud Carlos IIIMenzies Centre for Australian Studies, King's College London, University of LondonUniversity of California, DavisNational Institutes of HealthBijzonder Onderzoeksfonds UGentInstituut Born-BungeCentre for Medical Systems BiologyHjartaverndMarcus och Amalia Wallenbergs minnesfondElanJunta de AndalucíaUniversity of California, IrvineErasmus Medisch CentrumUniversity College London Hospitals NHS Foundation TrustMutuelle Générale de l'Education NationaleAgence Française de Sécurité Sanitaire des Produits de SantéMedical Research CouncilSwedish Brain PowerCorporación Tecnológica de AndalucíaNational Heart, Lung, and Blood InstituteNovartisNederlandse Organisatie voor Wetenschappelijk OnderzoekNorth Bristol NHS TrustDana FoundationVetenskapsrådetKuopion Yliopistollinen SairaalaKarolinska InstitutetFonds Wetenschappelijk OnderzoekAlzheimer's SocietyStichting MS ResearchFondation pour la Recherche MédicaleMedpaceNational Center for Advancing Translational SciencesBundesministerium für Bildung und ForschungUniversitat de BarcelonaAcademy of FinlandUniversity of CambridgeZonMwNewcastle UniversityNational Eye InstituteVlaamse regeringAlzheimer SocietyAustrian Science FundNational Institute for Health and Care ResearchCentro de Biología Molecular Severo OchoaUniversiteit AntwerpenNorthern California Institute for Research and EducationMedizinische Universität GrazFondation de FranceUniversity of PennsylvaniaU.S. Department of Veterans AffairsNational Institute on Deafness and Other Communication DisordersRush UniversityStockholms Läns LandstingUniversity of PittsburghWellcome TrustJohns Hopkins UniversityPfizerUniversity of WashingtonEmory UniversityYork UniversityVanderbilt UniversityOffice of Research and DevelopmentBelgian Federal Science Policy OfficeMassachusetts General HospitalGlaxoSmithKlineUniversity of MiamiNorthwestern UniversityGenentechAstraZenecaEuropean CommissionNational Institute of Environmental Health SciencesSchool of Medicine, Boston UniversityAlzheimer's AssociationInternationale Stichting Alzheimer OnderzoekSanofiEisaiUniversity of Southern CaliforniaMinistero della SaluteInstitut National de la Santé et de la Recherche MédicaleH. Lundbeck A/SKarl-Franzens-Universität GrazAlfried Krupp von Bohlen und Halbach-StiftungHoward Hughes Medical InstituteCardiff UniversityHersenstichtingEli Lilly and CompanyBristol-Myers Squibb
KeywordsApolipoprotein ESingle-nucleotide polymorphismGenome-wide association studyDementiaSNPGenotypeLocus (genetics)Alzheimer's diseaseGeneticsGenetic associationBiologyAlleleOncologyDiseaseInternal medicineMedicineGene
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 score0.003
Threshold uncertainty score0.011
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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 head0.305
Teacher spread0.270 · 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
Citations309
Published2015
Admission routes2
Has abstractno