TY - JOUR
T1 - Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations
AU - Nicolas, Aude
AU - Sherva, Richard
AU - Grenier-Boley, Benjamin
AU - Kim, Yoontae
AU - Kikuchi, Masataka
AU - Timsina, Jigyasha
AU - de Rojas, Itziar
AU - Dalmasso, María Carolina
AU - Zhou, Xiaopu
AU - Le Guen, Yann
AU - Arboleda-Bustos, Carlos E
AU - Camargos Bicalho, Maria Aparecida
AU - Guerchet, Maëlenn
AU - van der Lee, Sven
AU - Goss, Monica
AU - Castillo, Atahualpa
AU - Bellenguez, Céline
AU - Küçükali, Fahri
AU - Satizabal, Claudia L
AU - Fongang, Bernard
AU - Yang, Qiong
AU - Peters, Oliver
AU - Schneider, Anja
AU - Dichgans, Martin
AU - Rujescu, Dan
AU - Scherbaum, Norbert
AU - Deckert, Jürgen
AU - Riedel-Heller, Steffi
AU - Hausner, Lucrezia
AU - Molina-Porcel, Laura
AU - Düzel, Emrah
AU - Grimmer, Timo
AU - Wiltfang, Jens
AU - Heilmann-Heimbach, Stefanie
AU - Moebus, Susanne
AU - Tegos, Thomas
AU - Scarmeas, Nikolaos
AU - Dols-Icardo, Oriol
AU - Moreno, Fermin
AU - Pérez-Tur, Jordi
AU - Bullido, María J
AU - Pastor, Pau
AU - Sánchez-Valle, Raquel
AU - Álvarez, Victoria
AU - Cao, Han
AU - Ip, Nancy Y
AU - Fu, Amy K Y
AU - Rasmussen, Katrine Laura
AU - Thomassen, Jesper Qvist
AU - Frikke-Schmidt, Ruth
AU - EADB
A2 - Tybjærg-Hansen, Anne
N1 - © 2025. The Author(s).
PY - 2025/7
Y1 - 2025/7
N2 - 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.
AB - 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.
KW - Aged
KW - Alzheimer Disease/genetics
KW - Apolipoproteins E/genetics
KW - Biomarkers/cerebrospinal fluid
KW - Europe/epidemiology
KW - Female
KW - Genetic Predisposition to Disease
KW - Genetic Risk Score
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Multifactorial Inheritance/genetics
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - White People/genetics
UR - https://www.scopus.com/pages/publications/105012312720
U2 - 10.1038/s41588-025-02227-w
DO - 10.1038/s41588-025-02227-w
M3 - Journal article
C2 - 40533518
SN - 1061-4036
VL - 57
SP - 1598
EP - 1610
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -