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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Jean‐Charles Lambert, Carla A. Ibrahim‐Verbaas, Denise Harold, Adam C. Naj, Rebecca Sims, Céline Bellenguez, Gyungah Jun, Anita L. DeStefano, Gary W. Beecham, Benjamin Grenier‐Boley, Giancarlo Russo, Tricia A. Thornton‐Wells, Nicola Jones, Albert V. Smith, Vincent Chouraki, Charlene Thomas, M. Arfan Ikram, Diana Zélénika, Badri N. Vardarajan, Chiao‐Feng Lin, Amy Gerrish, Helena Schmidt, Brian W. Kunkle, Melanie Dunstan, Agustı́n Ruiz, Marie‐Thérèse Bihoreau, Seung‐Hoan Choi, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Alfredo Ramı́rez, Olivier Hanon, Annette L. Fitzpatrick, Joseph D. Buxbaum, Dominique Campion, Paul K. Crane, Clinton T. Baldwin, Tim Becker, Vilmundur Guðnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Philip L. De Jager, Vincent Deramecourt, Janet Johnston, Denis A. Evans, Simon Lovestone, Luc Letenneur, Francisco Jesús Morón, David C. Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison Goate, Nathalie Fiévet, Matthew J. Huentelman, Michael Gill, Kristelle Brown, M. Ilyas Kamboh, Lina Keller, Pascale Barberger‐Gateau, Bernadette McGuinness, Eric B. Larson, Robert C. Green, Amanda Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George‐Hyslop, Jordi Clarimón, Alberto Lleó, Debby W. Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petroula Proitsi, John Collinge, Sandro Sorbi, Florentino Sánchez-García, Nick C. Fox, John Hardy, María Cándida Déniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Michelangelo Mancuso, Fiona E. Matthews, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, María J. Bullido, Francesco Panza, Paolo Caffarra, Benedetta Nacmias, John R. Gilbert, Manuel Mayhaus, Lars Lannfelt, Håkon Håkonarson, Sabrina Pichler, Minerva M. Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Álvarez, Fanggeng Zou, Otto Valladares, Steven G. Younkin, Eliécer Coto, Kara L. Hamilton‐Nelson, Wei Gu, Cristina Razquín, Pau Pástor, Ignacio Mateo, Michael J. Owen, Kelley M. Faber, Pálmi V. Jónsson, Onofre Combarros, Michael O‘Donovan, Laura B. Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H. Mosley, David Bennett, Tamara B. Harris, Laura Fratiglioni, Clive Holmes, Renée F.A.G. de Bruijn, Peter Passmore, Thomas J. Montine, Karolien Bettens, Jerome I. Rotter, Alexis Brice, Kevin Morgan, Tatiana Foroud, Walter A. Kukull, Didier Hannequin, John Powell, Michael A. Nalls, Karen Ritchie, Kathryn L. Lunetta, John S.K. Kauwe, Eric Boerwinkle, Merçé Boada, Mikko Hiltunen, Eden R. Martin, Reinhold Schmidt, Dan Rujescu, Li‐San Wang, Jean‐François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M. Nöthen, Caroline Graff, Bruce M. Psaty, Lesley Jones, Jonathan L. Haines, Peter Holmans, Mark Lathrop, Margaret A. Pericak‐Vance, Lenore J. Launer, Lindsay A. Farrer, Cornelia M. van Duijn, Christine Van Broeckhoven, Valentina Moskvina, Sudha Seshadri, Julie Williams, Gerard D. Schellenberg, Philippe Amouyel
Bibliographic record
VenueNature Genetics · 2013
Typereview
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOccupational Cancer Research CentreMcGill University and Génome Québec Innovation CentreUniversity of Toronto
FundersNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNational Center for Advancing Translational SciencesMedical Research CouncilHjartaverndNational Institutes of HealthKarl-Franzens-Universität GrazPerelman School of Medicine, University of PennsylvaniaHáskóli ÍslandsErasmus Medisch CentrumInstitut National de la Santé et de la Recherche MédicaleAgence Nationale de la RechercheVersus ArthritisCardiff UniversityNational Institute on AgingNational Institute for Health and Care ResearchUniversity of MiamiWellcome TrustDr. John T. MacDonald FoundationDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseMedizinische Universität GrazAlzheimer's AssociationLlywodraeth CymruUniversity of WashingtonSchool of Medicine, Boston UniversityVanderbilt UniversityUniversität ZürichUniversity of Pennsylvania
KeywordsGenome-wide association studySingle-nucleotide polymorphismApolipoprotein EDiseaseBiologyAlzheimer's diseaseGenetic associationGeneticsMeta-analysisLocus (genetics)GenotypeMedicineGeneInternal 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)0.004
metaresearch head score (Gemma)0.008
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: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.022
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.008 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.010 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 head0.178
GPT teacher head0.429
Teacher spread0.252 · 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
Citations4,659
Published2013
Admission routes1
Has abstractno