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Record W4404995179 · doi:10.1038/s41380-024-02838-5

X‐chromosome-wide association study for Alzheimer’s disease

2024· article· en· W4404995179 on OpenAlexaff
Julie Le Borgne, Lissette Gomez, Sami Heikkinen, Najaf Amin, Shahzad Ahmad, Seung Hoan Choi, Joshua C. Bis, Benjamin Grenier‐Boley, Omar Garcia Rodriguez, Luca Kleineidam, Juan I. Young, Kumar Parijat Tripathi, Lily Wang, Achintya Varma, Rafael Campos-Martín, Sven J. van der Lee, Vincent Damotte, Itziar de Rojas, Sagnik Palmal, Richard B. Lipton, Eric M. Reiman, Ann C. McKee, Philip L. De Jager, William S. Bush, Scott A. Small, Allan I. Levey, Andrew J. Saykin, Tatiana Foroud, Marilyn Albert, Bradley T. Hyman, Ronald C. Petersen, Steven G. Younkin, Mary Sano, Thomas Wısnıewskı, Robert Vassar, Julie A. Schneider, Victor W. Henderson, Erik D. Roberson, Charles DeCarli, Frank M. LaFerla, James Brewer, Russell H. Swerdlow, Linda J. Van Eldik, Kara L. Hamilton‐Nelson, Henry L. Paulson, Adam C. Naj, Oscar L. López, Helena C. Chui, Paul K. Crane, Thomas J. Grabowski, Walter A. Kukull, Sanjay Asthana, Suzanne Craft, Stephen M. Strittmatter, Carlos Cruchaga, James B. Leverenz, Alison Goate, M. Ilyas Kamboh, Peter St George‐Hyslop, Otto Valladares, Amanda B Kuzma, Laura Cantwell, John C. Morris, Susan Slifer, Carolina Dalmasso, Atahualpa Castillo-Morales, Fahri Küçükali, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Jürgen Deckert, Steffi G. Riedel‐Heller, Lucrezia Hausner, Laura Molina‐Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann‐Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Oriol Dols‐Icardo, Fermín Moreno, Jordi Pérez‐Tur, María J. Bullido, Pau Pástor, Raquel Sánchez‐Valle, Victoria Álvarez, Merçé Boada, Pablo García‐González, Raquel Puerta, Pablo Mir, Luís Miguel Real, Gerard Piñol‐Ripoll, José María García‐Alberca, José Luís Royo, Eloy Rodríguez‐Rodríguez, Hilkka Soininen, Alexandre de Mendonça, Shima Mehrabian, Latchezar Traykov, Jakub Hort, Martin Vyhnálek, Jesper Qvist Thomassen, Yolande A.L. Pijnenburg, Henne Holstege, John van Swieten, Inez H.G.B. Ramakers, Frans Verhey, Philip Scheltens, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Jean-François Deleuze, Gaël Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Roberta Ghidoni, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Marco Spallazzi, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Paola Bossù, Carlo Masullo, Giacomina Rossi, Frank Jessen, María Victoria Fernández, Patrick G. Kehoe, Ruth Frikke‐Schmidt, Magda Tsolaki, Pascual Sánchez‐Juan, Kristel Sleegers, Martin Ingelsson, Jonathan L. Haines, Lindsay A. Farrer, Richard Mayeux, Li‐San Wang, Rebecca Sims, Anita L. DeStefano, Gerard D. Schellenberg, Sudha Seshadri, Philippe Amouyel, Julie Williams, Wiesje M. van der Flier, Alfredo Ramı́rez, Margaret A. Pericak‐Vance, Ole A. Andreassen, Cornelia M. van Duijn, Mikko Hiltunen, Agustı́n Ruiz, Josée Dupuis, Eden R. Martin, Jean‐Charles Lambert, Brian W. Kunkle, Céline Bellenguez

Bibliographic record

VenueMolecular Psychiatry · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsOntario Brain InstituteOccupational Cancer Research CentreUniversity of TorontoMcGill UniversityUniversity Health Network
FundersNational Institute on AgingMedical Research CouncilInstitut National de la Santé et de la Recherche MédicaleNational Heart, Lung, and Blood InstituteFondation pour la Recherche sur AlzheimerUniversité de LilleAgence Nationale de la RechercheDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
KeywordsPseudoautosomal regionGeneticsX chromosomeX-inactivationChromosomeDiseaseGenetic associationBiologyAlzheimer's diseaseGenome-wide association studyY chromosomeGeneMedicineGenotypeSingle-nucleotide polymorphismInternal medicine

Abstract

fetched live from OpenAlex

Abstract Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10− 8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10− 6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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)0.002
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.009
GPT teacher head0.262
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine 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

Citations7
Published2024
Admission routes1
Has abstractyes

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