Transferability of European-derived Alzheimer’s disease polygenic risk scores across multiancestry populations
Aude Nicolas (Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Inserm)
Richard Sherva (Boston University, VA Boston Healthcare System)
Benjamin Grenier-Boley (Inserm, Université de Lille)
Yoontae Kim (Chosun University)
Masataka Kikuchi (University of Tokyo)
Jigyasha Timsina (Washington University School of Medicine)
Itziar de Rojas (National Institute of Health Carlos III, Universitat Internacional de Catalunya)
Marcel J.T. Reinders (TU Delft - Pattern Recognition and Bioinformatics)
Jean-Charles Lambert (Université de Lille)
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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.
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