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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.
Fuente: Nature Genetics, 2025, 57, 1598-1610
Publisher: Nature Publishing Group
Year of publication: 2025
No. of pages: 24
Publication type: Article
DOI: 10.1038/s41588-025-02227-w
ISSN: 1061-4036,1546-1718
Publication Url: https://doi.org/10.1038/s41588-025-02227-w
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NICOLAS, AUDE
SHERVA, RICHARD
GRENIER-BOLEY, BEJAMIN
DIMI, YOONTAE
KIKUCHI, MASATAKA
TIMSINA, JIGYASHA
ROJAS, ITZIAR DE
DALMASSO, MARÍA CAROLINA
ZHOU, XIAOPU
LE GUEN, YANN
ARBOLEDA-BUSTOS, CARLOS E.
APARECIDA, MARÍA
BICALHO, CAMARGOS
GUERCHET, MAËLENN
VAN DER LEE, SVEN
GOSS, MÓNICA
CASTILLO, ATAHUALPA
BELLENGUEZ, CÉLINE
ELOY MANUEL RODRIGUEZ RODRIGUEZ
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