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Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations
Univ Lille, RID AGE Facteurs Risque & Determinants Mol Maladi, Inst Pasteur Lille, Inserm,CHU Lille, Lille, France.;Sorbonne Univ, Hop Pitie La Salpetriere, AP HP, Inst Cerveau,Paris Brain Inst,ICM,CNRS,Inserm, Paris, France..
VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA.;Boston Univ, Dept Med Biomed Genet, Boston, MA USA..
Univ Lille, RID AGE Facteurs Risque & Determinants Mol Maladi, Inst Pasteur Lille, Inserm,CHU Lille, Lille, France..
Chosun Univ, BK FOUR Dept Integrat Biol Sci, Gwangju, South Korea..
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2025 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 57, no 7Article in journal (Refereed) Published
Abstract [en]

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.
Place, publisher, year, edition, pages
Springer Publishing Company, 2025. Vol. 57, no 7
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Medical Genetics and Genomics
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URN: urn:nbn:se:uu:diva-565104DOI: 10.1038/s41588-025-02227-wISI: 001511340900001PubMedID: 40533518Scopus ID: 2-s2.0-105012312720OAI: oai:DiVA.org:uu-565104DiVA, id: diva2:1990157
Note

Lena Kilander och Malin Löwenmark ingår i forskargruppen EADB.

Available from: 2025-08-19 Created: 2025-08-19 Last updated: 2025-08-21Bibliographically approved

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Giedraitis, VilmantasIngelsson, MartinKilander, LenaLöwenmark, Malin

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Zhou, XiaopuLe Guen, YannAlvarez, VictoriaGiedraitis, VilmantasSachdev, PerminderIngelsson, MartinRamirez, AlfredoKilander, LenaLöwenmark, Malin
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