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

作者：A. Nicolas, R. Sherva, B. Grenier‐Boley, Yoontae Kim, M. Kikuchi, J. Timsina, I. de Rojas, M. Dalmasso, Xiaopu Zhou, Y. le Guen, C. Arboleda-Bustos, M. A. Camargos Bicalho, Maëlenn Guerchet, Sven J. van der Lee, Monica Goss, Atahualpa Castillo, C. Bellenguez, Fahri Küçükali, C. Satizabal, Bernard Fongang, Qiong Yang, Oliver Peters, Anja Schneider, Martin Dichgans, D. Rujescu, N. Scherbaum, Jürgen Deckert, S. Riedel-Heller, Lucrezia Hausner, L. Molina-Porcel, E. Düzel, T. Grimmer, Jens Wiltfang, S. Heilmann-Heimbach, S. Moebus, Thomas Tegos, N. Scarmeas, Orio Dols-Icardo, F. Moreno, Jordi Pérez-Tur, M. J. Bullido, P. Pastor, R. Sánchez-Valle, V. Álvarez, Han Cao, N. Ip, Amy K Y Fu, Fanny C. F. Ip, N. Olivar, C. Muchnik, Carolina Cuesta, Lorenzo Campanelli, Patricia Solís, D. G. Politis, Silvia Kochen, L. I. Brusco, M. Boada, P. García-González, R. Puerta, Pablo Mir, L. Real, G. Piñol-Ripoll, J. M. García-Alberca, J. L. Royo, E. Rodríguez-Rodríguez, H. Soininen, Sami Heikkinen, A. de Mendonça, S. Mehrabian, Latchezar Traykov, J. Hort, M. Vyhnálek, K. Rasmussen, J. Thomassen, Y. Pijnenburg, H. Holstege, J. V. van Swieten, H. Seelaar, J. A. Claassen, Willemijn J. Jansen, I. Ramakers, F. Verhey, A. van der Lugt, P. Scheltens, J. Ortega-Rojas, Ana Gabriela Concha Mera, Maria F. Mahecha, Rodrigo Pardo, Gonzalo Arboleda, S. Bahrami, V. Fominykh, G. Selbæk, Caroline Graff, G. Papenberg, V. Giedraitis, A. Boland, J. Deleuze, L. de Marco, E. N. de Moraes, Bernardo de Mattos Viana, Marco Túlio Gualberto Cintra, Teresa Juárez-Cedillo, A. Griswold, Tatiana Forund, Jonathan Haines, L. Farrer, A. Destefano, Ellen M Wijsman, R. Mayeux, M. Pericak-Vance, B. Kunkle, A. Goate, G. Schellenberg, B. Vardarajan, Li-San Wang, Y. Leung, C. Dalgard, G. Nicolas, D. Wallon, C. Dufouil, Florence Pasquier, O. Hanon, S. Debette, E. Grünblatt, Julius Popp, Bárbara Angel, Sergio Gloger, María Victoria Chacón, Rafael Aránguiz, P. Orellana, A. Slachevsky, C. González-Billault, C. Albala, Patricio Fuentes, Perminder S. Sachdev, Karen A. Mather, R. Hauger, V. Merritt, M. Panizzon, Rui Zhang, J. Gaziano, Roberta Ghidoni, D. Galimberti, Beatrice Arosio, Patrizia Mecocci, V. Solfrizzi, L. Parnetti, A. Squassina, L. Tremolizzo, B. Borroni, B. Nacmias, Paolo Caffarra, D. Seripa, I. Rainero, A. Daniele, F. Piras, Sonia Najaf Peter A. Luca Dag Pablo Carla Emilio Daniel Moreno-Grau Amin Holmans Kleineidam Aarsland Garci, S. Moreno-Grau, Najaf Amin, P. Holmans, L. Kleineidam, D. Aarsland, P. García-González, C. Abdelnour, E. Alarcón‐Martín, Daniel Alcolea, M. Alegret, Ignacio Alvarez, N. J. Armstrong, Tsolaki Anthoula, I. Appollonio, M. Arcaro, S. Archetti, A. Arias Pastor, L. Athanasiu, H. Bailly, N. Banaj, M. Baquero, A. Pastor, Sonia Bellini, C. Berr, C. Besse, Valentina Bessi, G. Binetti, Alessandra Bizarro, R. Blesa, S. Boschi, P. Bossù, G. Bråthen, Catherine Bresner, H. Brodaty, K. Brookes, D. Buiza‐Rueda, K. Bûrger, V. Burholt, M. Calero, G. Chêne, A. Carracedo, R. Cecchetti, Laura Cervera-Carles, C. Charbonnier, C. Chillotti, Simona Ciccone, J. Clarimón, Christopher Clark, E. Conti, A. Corma-Gómez, G. M. Giuffré, C. Custodero, D. Daian, E. Dardiotis, P. D. de Deyn, T. del Ser, N. Denning, J. Diehl-Schmid, M. Diez-Fairen, P. Rossi, S. Djurovic, E. Duron, S. Engelborghs, A. Espinosa, M. Ewers, Tagliavini Fabrizio, S. Nielsen, L. Farotti, C. Fenoglio, M. Fernandez-Fuertes, Catarina B. Ferreira, E. Ferri, B. Fin, Peter Fischer, T. Fladby, K. Fliessbach, J. Fortea, T. Foroud, Silvia Fostinelli, Nick C. Fox, E. Franco-Macías, A. Frank‐García, Lutz Froelich, J. M. García-Alberca, S. García-Madrona, G. García-Ribas, I. Giegling, Giaccone Giorgio, O. Goldhardt, A. González-Pérez, Giulia Grande, Emma Green, T. Guetta-Baranes, A. Haapasalo, Georgios M. Hadjigeorgiou, Harald Hampel, J. Hardy, A. Hartmann, J. Harwood, S. Helisalmi, M. Heneka, Isabel Hernández, Martin J. Herrmann, Per Hoffmann, Clive Holmes, R. Huerto Vilas, M. Hulsman, G. Biessels, C. Johansson, L. Kilander, A. Ståhlbom, M. Kivipelto, A. Koivisto, J. Kornhuber, M. Kosmidis, C. Lage, E. Laukka, A. Lauria, J. Lehtisalo, O. Lerch, A. Lleó, Adolfo López-de Munain, Seth Love, Malin Löwemark, L. Luckcuck, J. Macías, Catherine A. MacLeod, W. Maier, F. Mangialasche, M. Spallazzi, M. Marquié, R. Marshall, Angel Martin Montes, C. Martínez Rodríguez, S. Mead, M. Medina, A. Meggy, S. Mendoza, M. Menéndez-González, M. Mol, L. Montrreal, K. Morgan, Markus M. Möthen, T. Ngandu, B. Nordestgaard, R. Olaso, A. Orellana, Michela Orsini, G. Ortega, Alessandro Padovani, A. Pérez-Cordón, Pierre Pericard, J. Pineda, C. Pisanu, Thomas Polak, D. Posthuma, Josef Priller, O. Quenez, I. Quintela, A. Rabano, M. Reinders, P. Riederer, N. Roberto, A. Rongve, I. Allende, M. Rosende-Roca, J. L. Royo, E. Rubino, M. Sáez, P. Sakka, I. Saltvedt, Á. Sanabria, M. Bernal Sánchez-Arjona, F. Sánchez-García, P. Sánchez-Juan, S. Sando, M. Scamosci, E. Scarpini, Martin Scherer, Matthias C. Schmid, Jonathan M. Schott, A. Shadrin, O. Skrobot, Alina Solomon, S. Sorbi, O. Sotolongo-Grau, A. Spottke, E. Stordal, Juan Pablo Tartan, L. Tárraga, N. Tesi, A. Thalamuthu, Tegos Thomas, A. Tybjærg-Hansen, A. Uitterlinden, Abbe Ullgren, I. Ulstein, S. Valero, C. van Broeckhoven, J. Van Dongen, Rik Vandenberghe, J. Vidal, Jonathan S. Vogelgsang, Michael Wagner, L. Weinhold, Gill Windle, Bob Woods, M. Yannakoulia, M. Zulaica, H. Leonard, J. Yokoyama, M. Nalls, A. Miyashita, N. Hara, K. Ozaki, S. Niida, Julie Williams, C. Masullo, P. Amouyel, P. Preux, P. Mbelesso, Bébène Bandzouzi, A. Saykin, Frank Jessen, P. Kehoe, Cornelia M. van Duijn, Nesrine Ben Salem, R. Frikke-Schmidt, L. Cherni, M. Greicius, Magdalini Tsolaki, M. A. Romano Silva, T. Porter, Simon M. Laws, K. Sleegers, M. Ingelsson, J. Dartigues, S. Seshadri, G. Rossi, Laura Morelli, M. Hiltunen, R. Sims, W. M. van der Flier, O. Andreassen, H. Arboleda, C. Cruchaga, V. Escott-Price, A. Ruiz, K. Lee, T. Ikeuchi, A. Ramírez, Jungsoo Gim, M. Logue, Jeanc Lambert · 发表于：Nature Genetics · 年份：2025 · DOI：10.1038/s41588-025-02227-w · 被引用次数：19 · 研究领域：Medicine

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.