Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations
Authors
Aude Nicolas, Richard Sherva, Benjamin Grenier-Boley, Yoontae Kim, Masataka Kikuchi, Jigyasha Timsina, Itziar de Rojas, María Carolina Dalmasso, Xiaopu Zhou, Yann Le Guen, Carlos E Arboleda-Bustos, Maria Aparecida Camargos Bicalho, Maëlenn Guerchet, Sven van der Lee, Monica Goss, Atahualpa Castillo, Céline Bellenguez, Fahri Küçükali, Claudia L Satizabal, Bernard Fongang, Qiong Yang, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Jürgen Deckert, Steffi 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, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Han Cao, Nancy Y Ip, Amy K Y Fu, Fanny C F Ip, Natividad Olivar, Carolina Muchnik, Carolina Cuesta, Lorenzo Campanelli, Patricia Solis, Daniel Gustavo Politis, Silvia Kochen, Luis Ignacio Brusco, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Sami Heikkinen, Alexandre de Mendonça, Shima Mehrabian, Latchezar Traykov, Jakub Hort, Martin Vyhnalek, 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 Ramakers, Frans Verhey, Aad van der Lugt, Philip Scheltens, Jenny Ortega-Rojas, Ana Gabriela Concha Mera, Maria F Mahecha, Rodrigo Pardo, Gonzalo 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 Juarez-Cedillo, Anthony J Griswold, Tatiana Forund, Jonathan Haines, Lindsay Farrer, Anita DeStefano, Ellen Wijsman, Richard Mayeux, Margaret Pericak-Vance, Brian Kunkle, Alison Goate, Gerard D Schellenberg, Badri Vardarajan, Li-San Wang, Yuk Yee Leung, Clifton L Dalgard, Gael Nicolas, David Wallon, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Bárbara Angel, Sergio Gloger, Maria Victoria Chacon, Rafael Aranguiz, Paulina Orellana, Andrea Slachevsky, Christian Gonzalez-Billault, Cecilia Albala, Patricio Fuentes, Perminder Sachdev, Karen A Mather, Richard L Hauger, Victoria Merritt, Matthew 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, EADB, Hampton L Leonard, Jenifer S Yokoyama, Mike A Nalls, Akinori Miyashita, Norikazu Hara, Kouichi Ozaki, Shumpei Niida, Julie Williams, Carlo Masullo, Philippe Amouyel, Pierre-Marie Preux, Pascal Mbelesso, Bébène Bandzouzi, Andy Saykin, Frank Jessen, Patrick G Kehoe, Cornelia Van Duijn, Nesrine Ben Salem, Ruth Frikke-Schmidt, Lotfi Cherni, Michael D Greicius, Magda Tsolaki, Pascual Sánchez-Juan, 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 van der Flier, Ole A Andreassen, Humberto Arboleda, Carlos Cruchaga, Valentina Escott-Price, Agustín Ruiz, Kun Ho Lee, Takeshi Ikeuchi, Alfredo Ramirez, Jungsoo Gim, Mark Logue, Jean-Charles Lambert
Nat Genet. 2025 Jun 18. doi: 10.1038/s41588-025-02227-w. Online ahead of print.
ABSTRACT
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.
