Transferability of a European-derived Alzheimer Disease Genetic Risk Score across Multi-Ancestry Populations.
Nicolas, A.; Grenier-Boley, B.; Sherva, R.; Kim, Y.; Kikuchi, M.; de Rojas, i.; Dalmasso, C.; Zhou, X.; Le Guen, Y.; Arboleda-Bustos, C. E.; Camargos Bicalho, M. A.; Guerchet, M.; van de Lee, S.; Goss, M.; castillo, a.; bellenguez, C.; Kucukali, F.; Satizabal Barrera, C.; Fongang, B.; yang, Q.; Peters, O.; Schneider, A.; Dichgans, M.; Rujescu, D.; Scherbaum, N.; Deckert, J.; Riedel-Heller, S.; Hausner, L.; Molina Porcel, L.; Duzel, E.; Grimmer, T.; Wiltfang, J.; Heilmann-Heimbach, S.; Moebus, S.; Tegos, T.; Scarmeas, N.; Dols-icardo, O.; Moreno, F.; Perez-Tur, J.; Bullido, M. J.; Pastor, P.; S
Show abstract
A polygenic score (PGS) for Alzheimers disease (AD) was recently derived 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 AD risk, age at onset, and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score (PRS) improved the association with AD risk in most of the multi-ancestry populations tested when the APOE region was included. Lastly, we found that the PGS/PRS, 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, but studies of more diverse populations are still needed for a better characterization of the AD genetics.
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