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Record W4411428667 · doi:10.1038/s41588-025-02227-w

Transferability of European-derived Alzheimer’s disease polygenic risk scores across multiancestry populations

2025· article· en· W4411428667 on OpenAlexaff
Aude Nicolas, Richard Sherva, Benjamin Grenier‐Boley, Y T Kim, Masataka Kikuchi, Jigyasha Timsina, Itziar de Rojas, Carolina Dalmasso, Xiaopu Zhou, Yann Le Guen, Carlos Bustos, Maria Aparecida Camargos Bicalho, Maëlenn Guerchet, Sven J. van der Lee, Monica Goss, Atahualpa Castillo-Morales, Céline Bellenguez, Fahri Küçükali, Claudia L. Satizábal, Bernard Fongang, Qiong Yang, 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, Han Cao, Nancy Y. Ip, Amy K.Y. Fu, Fanny C.F. Ip, Natividad Olivar, Carolina Muchnik, Carolina De La Cuesta, Lorenzo Campanelli, Patricia Solís, Daniel Gustavo Politis, Silvia Kochen, Luis Ignacio Brusco, 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, Sami Heikkinen, Alexandre de Mendonça, Shima Mehrabian, Latchezar Traykov, Jakub Hort, Martin Vyhnálek, Katrine Laura Rasmussen, Jesper Qvist Thomassen, Yolande A.L. Pijnenburg, Henne Holstege, John C. van Swieten, Harro Seelaar, Jurgen A.H.R. Claassen, Willemijn J. Jansen, Inez H.G.B. Ramakers, Frans R.J. Verhey, Aad van der Lugt, Philip Scheltens, Jenny Ortega-Rojas, Ana Gabriela Concha Mera, María F. Mahecha, Rodrigo Pardo, Gonzálo Arboleda, Shahram Bahrami, Vera Fominykh, Geir Selbæk, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Jean‐François Deleuze, Luiz Armando De Marco, Edgar Nunes de Moraes, Bernardo de Mattos Viana, Marco Túlio Gualberto Cintra, Teresa Juárez‐Cedillo, Anthony J. Griswold, Tatiana Forund, Jonathan L. Haines, Lindsay A. Farrer, Anita L. DeStefano, Ellen M. Wijsman, Richard Mayeux, Margaret A. Pericak‐Vance, Brian W. Kunkle, Alison Goate, Gerard D. Schellenberg, Badri N. Vardarajan, Li-San Wang, Yuk Yee Leung, Clifton L. Dalgard, Gaël Nicolas, David Wallon, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Bárbara Ángel, Sergio Gloger, María Victoria Chacón, Rafael Aránguiz, Paulina Orellana, Andrea Slachevsky, Christian González‐Billault, Cecilia Albala, Patricio Fuentes, Perminder S. Sachdev, Karen A. Mather, Richard L. Hauger, Victoria C. Merritt, Matthew S. Panizzon, Rui Zhang, J. Michael Gaziano, Roberta Ghidoni, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Fabrizio Piras, Pascual Sánchez‐Juan, Hampton L. Leonard, Jennifer S. Yokoyama, Mike A. Nalls, Akinori Miyashita, Norikazu Hara, Kouichi Ozaki, Shumpei Niida, Julie Williams, Carlo Masullo, Philippe Amouyel, Pierre‐Marie Preux, Pascal M'Belesso, Bébène Bandzouzi, Andrew J. Saykin, Frank Jessen, Patrick G. Kehoe, Cornelia M. van Duijn, Nesrine Ben Salem, Ruth Frikke‐Schmidt, Lotfi Cherni, Michael D. Greicius, Magda Tsolaki, Marco Aurélio Romano‐Silva, Tenielle Porter, Simon M. Laws, Kristel Sleegers, Martin Ingelsson, Jean‐François Dartigues, Sudha Seshadri, Giacomina Rossi, Laura Morelli, Mikko Hiltunen, Rebecca Sims, Wiesje M. van der Flier, Ole A. Andreassen, Humberto Arboleda, Carlos Cruchaga, Valentina Escott‐Price, Agustı́n Ruiz, Kun Ho Lee, Takeshi Ikeuchi, Alfredo Ramı́rez, Mark W. Logue, Jean‐Charles Lambert

Bibliographic record

VenueNature Genetics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOntario Brain InstituteOccupational Cancer Research CentreUniversity Health Network
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingNational Heart, Lung, and Blood InstituteFondation pour la Recherche sur AlzheimerFondation pour la Recherche MédicaleInstitut National de la Santé et de la Recherche MédicaleU.S. Department of Veterans AffairsEU Joint Programme – Neurodegenerative Disease ResearchUniversité de LilleDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
KeywordsBiologyPolygenic risk scoreGenome-wide association studyApolipoprotein EGenetic associationDiseaseGeneticsLocus (genetics)AlleleSingle-nucleotide polymorphismGenotypeGeneInternal medicineMedicine

Abstract

fetched live from OpenAlex

A polygenic score (PGS) for Alzheimer’s disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score improved the association with the AD risk in most of the multiancestry populations tested when the APOE region was included. Finally, we found that the PGS/polygenic risk score captured AD-specific information because the association weakened as the diagnosis was broadened. In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, although studies of more diverse populations are still needed to better characterize the genetics of AD. Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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)0.016
metaresearch head score (Gemma)0.042
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 score0.016
Threshold uncertainty score0.087

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0160.042
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.021
GPT teacher head0.331
Teacher spread0.310 · 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

Citations17
Published2025
Admission routes1
Has abstractyes

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