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