← Back to cohort
Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Brian W. Kunkle, Benjamin Grenier‐Boley, Rebecca Sims, Joshua C. Bis, Vincent Damotte, Adam C. Naj, Anne Boland, Maria Vronskaya, Sven J. van der Lee, Alexandre Amlie‐Wolf, Céline Bellenguez, Aura Frizatti, Vincent Chouraki, Eden R. Martin, Kristel Sleegers, Nandini Badarinarayan, Jóhanna Jakobsdóttir, Kara L. Hamilton‐Nelson, Sonia Moreno–Grau, Robert Olaso, Rachel Raybould, Yuning Chen, Amanda B Kuzma, Mikko Hiltunen, Taniesha Morgan, Shahzad Ahmad, Badri N. Vardarajan, Jacques Epelbaum, Per Hoffmann, Merçé Boada, Gary W. Beecham, Jean-Guillaume Garnier, Denise Harold, Annette L. Fitzpatrick, Otto Valladares, Marie-Laure Moutet, Amy Gerrish, Albert V. Smith, Liming Qu, Delphine Bacq, Nicola Denning, Xueqiu Jian, Yi Zhao, Maria Del Zompo, Nick C. Fox, Seung‐Hoan Choi, Ignacio Mateo, Joseph T. Hughes, Hieab H.H. Adams, John Malamon, Florentino Sánchez-García, Yogen Patel, Jennifer A. Brody, Beth A. Dombroski, María Cándida Déniz Naranjo, Makrina Daniilidou, Guðný Eiríksdóttir, Shubhabrata Mukherjee, David Wallon, James Uphill, Thor Aspelund, Laura B. Cantwell, Fabienne Garzia, Daniela Galimberti, Edith Hofer, Mariusz Butkiewicz, Bertrand Fin, Elio Scarpini, Chloé Sarnowski, William S. Bush, Stéphane Meslage, Johannes Kornhuber, Charles C. White, Robert C. Barber, Sebastiaan Engelborghs, Sabrina Sordon, Dina Voijnovic, Perrie M. Adams, Rik Vandenberghe, Manuel Mayhaus, L. Adrienne Cupples, Marilyn S. Albert, Peter Paul De Deyn, Wei Gu, J.J. Himali, Duane Beekly, Alessio Squassina, Annette M. Hartmann, Adelina Orellana, Deborah Blacker, Eloy Rodríguez‐Rodríguez, Simon Lovestone, Melissa E. Garcia, Rachelle S. Doody, Carmen Munoz-Fernadez, Rebecca Sussams, Honghuang Lin, Thomas Fairchild, Yolanda A. Benito, Clive Holmes, Hata Karamujić‐Čomić, Matthew P. Frosch, Håkan Thonberg, Wolfgang Maier, Gennady V. Roshchupkin, Bernardino Ghetti, Vilmantas Giedraitis, Amit Kawalia, Shuo Li, Ryan Huebinger, Lena Kilander, Susanne Moebus, Isabel Hernández, M. Ilyas Kamboh, RoseMarie Brundin, James Turton, Qiong Yang, Mindy J. Katz, Letizia Concari, Jenny Lord, Alexa S. Beiser, C. Dirk Keene, Seppo Helisalmi, Iwona Kłoszewska, Walter A. Kukull, Anne M. Koivisto, Aoibhinn Lynch, Lluís Tárraga, Eric B. Larson, Annakaisa Haapasalo, Brian Lawlor, Richard B. Lipton, Vincenzo Solfrizzi, Michael Gill, W. T. Longstreth, Thomas J. Montine, Vincenza Frisardi, Mónica Díez-Fairén, Fernando Rivadeneira, Ronald C. Petersen, Vincent Deramecourt, Ignacio Álvarez, Francesca Salani, Antonio Ciaramella, Eric Boerwinkle, Eric M. Reiman, Nathalie Fiévet, Jerome I. Rotter, Joan Reisch, Olivier Hanon, Chiara Cupidi, André G. Uitterlinden, Donald R. Royall, Carole Dufouil, Raffaele Maletta, Itziar de Rojas, Mary Sano, Alexis Brice, Roberta Cecchetti, Peter St George‐Hyslop, Karen Ritchie, Magda Tsolaki, Debby W. Tsuang, Bruno Dubois, David Craig, Chuang‐Kuo Wu, Hilkka Soininen, Despoina Avramidou, Roger L. Albin, Laura Fratiglioni, Antonia Germanou, Liana G. Apostolova, Lina Keller, Maria Koutroumani, Steven E. Arnold, Francesco Panza, Olymbia Gkatzima, Sanjay Asthana, Didier Hannequin, Patrice L. Whitehead, Craig Atwood, Paolo Caffarra, Harald Hampel, Inés Quintela, Ãngel Carracedo, Lars Lannfelt, David C. Rubinsztein, Lisa L. Barnes, Florence Pasquier, Lutz Frölich, Sandra Barral, Bernadette McGuinness, Thomas G. Beach, Janet Johnston, James T. Becker, Peter Passmore, Eileen H. Bigio, Jonathan M. Schott, Thomas D. Bird, Jason D. Warren, Bradley F. Boeve, Michelle K. Lupton, James D. Bowen, Adam Boxer, John Powell, James R. Burke, John S.K. Kauwe, Jeffrey M. Burns, Michelangelo Mancuso, Joseph D. Buxbaum, Ubaldo Bonuccelli, Nigel J. Cairns, Andrew McQuillin, Chuanhai Cao, Gill Livingston, Chris Carlson, Nicholas Bass, Cynthia M. Carlsson, John Hardy, Regina M. Carney, José Brás, Minerva M. Carrasquillo, Rita Guerreiro, Mariet Allen, Helena C. Chui, Elizabeth Fisher, Carlo Masullo, Elizabeth Crocco, Charles DeCarli, Gina Bisceglio, Malcolm Dick, Li Ma, Ranjan Duara, Neill R. Graff‐Radford, Denis A. Evans, Angela Hodges, Kelley M. Faber, Martin Scherer, Kenneth B. Fallon, David W. Fardo, Reinhard Heun, Martin R. Farlow, Heike Kölsch, Steven H. Ferris, Markus Leber, Tatiana Foroud, Isabella Heuser, Douglas Galasko, Ina Giegling, Marla Gearing, Michael Hüll, Daniel H. Geschwind, John R. Gilbert, John C. Morris, Robert C. Green, Kevin H. Mayo, John H. Growdon, Thomas Feulner, Ronald L. Hamilton, Lindy E. Harrell, Dmitriy Drichel, Lawrence S. Honig, Thomas D. Cushion, Matthew J. Huentelman, Paul Hollingworth, Christine M. Hulette, Bradley T. Hyman, Iain Marshall, Gail P. Jarvik, Alun Meggy, Erin L. Abner, Georgina Menzies, Lee‐Way Jin, Ganna Leonenko, Luís Miguel Real, Gyungah R Jun, Clinton T. Baldwin, Detelina Grozeva, Anna Karydas, Giancarlo Russo, Ronald Kim, Frank Jessen, Neil W. Kowall, Bruno Vellas, Joel H. Kramer, Emma Vardy, Frank M. LaFerla, Karl‐Heinz Jöckel, James J. Lah, Martin Dichgans, James B. Leverenz, David Mann, Allan I. Levey, Stuart Pickering‐Brown, Andrew P. Lieberman, Norman Klopp, Kathryn L. Lunetta, H.‐Erich Wichmann, Constantine G. Lyketsos, Kevin Morgan, Daniel Marson, Kristelle Brown, Frank Martiniuk, Christopher Medway, Deborah C. Mash, Markus M. Nöthen, Eliezer Masliah, Nigel M. Hooper, Wayne C. McCormick, Antonio Daniele, Susan M. McCurry, Andrew McDavid, John Gallacher, Ann C. McKee, Hendrik van den Bussche, Marsel Mesulam, Carol Brayne, Bruce L. Miller, Steffi G. Riedel‐Heller, Carol A. Miller, Joshua W. Miller, Ammar Al‐Chalabi, Christopher E. Shaw, Amanda Myers, Jens Wiltfang, Sid E. O’Bryant, John Olichney, Victoria Álvarez, Joseph E. Parisi, Andrew B. Singleton, Henry L. Paulson, John Collinge, William Perry, Simon Mead, Elaine R. Peskind, David H. Cribbs, Martin N. Rossor, Aimee Pierce, Natalie S. Ryan, Wayne W. Poon, Benedetta Nacmias, Huntington Potter, Sandro Sorbi, Joseph F. Quinn, Eleonora Sacchinelli, Ashok Raj, Gianfranco Spalletta, Murray A. Raskind, Carlo Caltagirone, Paola Bossù, Maria Donata Orfei, Barry Reisberg, Robert Clarke, Christiane Reitz, A. David Smith, John M. Ringman, Donald Warden, Erik D. Roberson, Gordon Wilcock, Ekaterina Rogaeva, Amalia C. Bruni, Howard J. Rosen, Maura Gallo, Roger N. Rosenberg, Yoav Ben‐Shlomo, Mark A. Sager, Patrizia Mecocci, Andrew J. Saykin, Pau Pástor, Michael L. Cuccaro, Jeffery M. Vance, Julie A. Schneider, Lori S. Schneider, Susan Slifer, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Russell H. Swerdlow, Mitchell Tang, Rudolph E. Tanzi, 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, Yasaman Saba, Alberto Pilotto, María J. Bullido, Oliver Peters, Paul K. Crane, David A. Bennett, Paola Bosco, Eliécer Coto, Virginia Boccardi, Phil L. De Jager, Alberto Lleó, Martin Ingelsson, Panos Deloukas, Carlos Cruchaga, Caroline Graff, Rhian Gwilliam, Myriam Fornage, Alison Goate, Pascual Sánchez‐Juan, Patrick G. Kehoe, Najaf Amin, Claudine Berr, Stéphanie Debette, Seth Love, Lenore J. Launer, Steven G. Younkin, Jean‐François Dartigues, Chris Corcoran, M. Arfan Ikram, Dennis W. Dickson, Gaël Nicolas, Dominique Campion, JoAnn T. Tschanz, Helena Schmidt, Håkon Håkonarson, Jordi Clarimón, Ron Munger, Reinhold Schmidt, Lindsay A. Farrer, Christine Van Broeckhoven, Michael O‘Donovan, Anita L. DeStefano, Lesley Jones, Jonathan L. Haines, Jean-François Deleuze, Michael J. Owen, Vilmundur Guðnason, Richard Mayeux, Valentina Escott‐Price, Bruce M. Psaty, Alfredo Ramı́rez, Li-San Wang, Agustı́n Ruiz, Cornelia M. van Duijn, Peter Holmans, Sudha Seshadri, Julie Williams, Philippe Amouyel, Gerard D. Schellenberg, Jean‐Charles Lambert, Margaret A. Pericak‐Vance
Bibliographic record
VenueNature Genetics · 2019
Typereview
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Institute of Neurological Disorders and StrokeMedical Research CouncilAgence Nationale de la RechercheNational Center for Advancing Translational SciencesRosetrees TrustMotor Neurone Disease AssociationParkinson's UKNational Institute for Health and Care ResearchWellcome Trust
KeywordsBiologyImmunityDiseaseGeneticsAlzheimer's diseaseMeta-analysisBioinformaticsEvolutionary biologyComputational biologyImmune systemInternal 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)0.002
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.013
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.005 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 head0.102
GPT teacher head0.402
Teacher spread0.300 · 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 designMeta-analysis
Domainnot available
GenreReview
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
Citations3,204
Published2019
Admission routes1
Has abstractno