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

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

 Editorial: Nature Publishing Group

 Año de publicación: 2025

 Nº de páginas: 24

 Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41588-025-02227-w

 ISSN: 1061-4036,1546-1718

 Url de la publicación: https://doi.org/10.1038/s41588-025-02227-w

Autoría

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