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

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 flu...

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Authors: Nicolas, A; Sherva, R; Grenier-Boley, B; Kim, Y; Kikuchi, M; Timsina, J; de Rojas, I; Dalmasso, MC; Zhou, XP; Le Guen, Y; Arboleda-Bustos, CE; Bicalho, MAC; Guerchet, M; van der Lee, S; Goss, M; Castillo, A; Bellenguez, C; Küçükali, F; Satizabal, CL; Fongang, B; Yang, Q; Peters, O; Schneider, A; Dichgans, M; Rujescu, D; Scherbaum, N; Deckert, J; Riedel-Heller, S; Hausner, L; Molina-Porcel, L; Duezel, E; Grimmer, T; Wiltfang, J; Heilmann-Heimbach, S; Moebus, S; Tegos, T; Scarmeas, N; Dols-Icardo, O; Moreno, F; Pérez-Tur, J; Bullido, MJ; Pastor, P; Sánchez-Valle, R; Alvarez, V; Cao, H; Ip, NY; Fu, AKY; Ip, FCF; Olivar, N; Muchnik, C; Cuesta, C; Campanelli, L; Solis, P; Politis, DG; Kochen, S; Brusco, LI; Boada, M; García-González, P; Puerta, R; Mir, P; Real, LM; Pinol-Ripoll, G; García-Alberca, JM; Royo, JL; Rodriguez-Rodriguez, E; Soininen, H; Heikkinen, S; de Mendonça, A; Mehrabian, S; Traykov, L; Hort, J; Vyhnalek, M; Rasmussen, KL; Thomassen, JQ; Pijnenburg, YAL; Holstege, H; van Swieten, JC; Seelaar, H; Claassen, JAHR; Jansen, WJ; Ramakers, I; Verhey, F; van der Lugt, A; Scheltens, P; Ortega-Rojas, J; Mera, AGC; Mahecha, MF; Pardo, R; Arboleda, G; Bahrami, S; Fominykh, V; Selbaek, G; Graff, C; Papenberg, G; Giedraitis, V; Boland, A; Deleuze, JF; de Marco, LA; de Moraes, EN; Viana, BD; Cintra, MTG; Juarez-Cedillo, T; Griswold, AJ; Forund, T; Haines, J; Farrer, L; Destefano, A; Wijsman, E; Mayeux, R; Pericak-Vance, M; Kunkle, B; Goate, A; Schellenberg, GD; Vardarajan, B; Wang, LS; Leung, YY; Dalgard, CL; Nicolas, G; Wallon, D; Dufouil, C; Pasquier, F; Hanon, O; Debette, S; Gruenblatt, E; Popp, J; Angel, B; Gloger, S; Chacon, MV; Aranguiz, R; Orellana, P; Slachevsky, A; Gonzalez-Billault, C; Albala, C; Fuentes, P; Sachdev, P; Mather, KA; Hauger, RL; Merritt, V; Panizzon, M; Zhang, R; Gaziano, JM; Ghidoni, R; Galimberti, D; Arosio, B; Mecocci, P; Solfrizzi, V; Parnetti, L; Squassina, A; Tremolizzo, L; Borroni, B; Nacmias, B; Caffarra, P; Seripa, D; Rainero, I; Daniele, A; Piras, F; Leonard, HL; Yokoyama, JS; Nalls, MA; Miyashita, A; Hara, N; Ozaki, K; Niida, S; Williams, J; Masullo, C; Amouyel, P; Preux, PM; Mbelesso, P; Bandzouzi, B; Saykin, A; Jessen, F; Kehoe, PG; Van Duijn, C; Ben Salem, N; Frikke-Schmidt, R; Cherni, L; Greicius, MD; Tsolaki, M; Sánchez-Juan, P; Silva, MAR; Porter, T; Laws, SM; Sleegers, K; Ingelsson, M; Dartigues, JF; Seshadri, S; Rossi, G; Morelli, L; Hiltunen, M; Sims, R; van der Flier, W; Andreassen, OA; Arboleda, H; Cruchaga, C; Escott-Price, V; Ruiz, A; Lee, KH; Ikeuchi, T; Ramirez, A; Gim, J; Logue, M; Lambert, JC
Format: Article
Status:Published version
Publication date:2025
Country:España
Institution:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repository:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:dnet:r-fisabio___::28773980ce39cb259e439e00c4ac26b7
Online Access:https://fisabio.portalinvestigacion.com/publicaciones/21026
Access Level:Open access
Description
Summary: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.