Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.
Nicolas A., Sherva R., Grenier-Boley B., Kim Y., Kikuchi M., Timsina J., de Rojas I., Dalmasso MC., Zhou X., Le Guen Y., Arboleda-Bustos CE., Camargos Bicalho MA., Guerchet M., van der Lee S., Goss M., Castillo A., Bellenguez C., Küçükali F., Satizabal CL., Fongang B., Yang Q., Peters O., Schneider A., Dichgans M., Rujescu D., Scherbaum N., Deckert J., Riedel-Heller S., Hausner L., Molina-Porcel L., Düzel E., Grimmer T., Wiltfang J., Heilmann-Heimbach S., Moebus S., Tegos T., Scarmeas N., Dols-Icardo O., Moreno F., Pérez-Tur J., Bullido MJ., Pastor P., Sánchez-Valle R., Álvarez V., Cao H., Ip NY., Fu AKY., Ip FCF., Olivar N., Muchnik C., Cuesta C., Campanelli L., Solis P., Politis DG., Kochen S., Brusco LI., Boada M., García-González P., Puerta R., Mir P., Real LM., Piñol-Ripoll G., García-Alberca JM., Royo JL., Rodriguez-Rodriguez E., Soininen H., Heikkinen S., de Mendonça A., Mehrabian S., Traykov L., Hort J., Vyhnalek M., Rasmussen KL., Thomassen JQ., Pijnenburg YAL., Holstege H., van Swieten JC., Seelaar H., Claassen JAHR., Jansen WJ., Ramakers I., Verhey F., van der Lugt A., Scheltens P., Ortega-Rojas J., Concha Mera AG., Mahecha MF., Pardo R., Arboleda G., Bahrami S., Fominykh V., Selbæk G., Graff C., Papenberg G., Giedraitis V., Boland A., Deleuze J-F., de Marco LA., de Moraes EN., de Mattos Viana B., Túlio Gualberto Cintra M., Juarez-Cedillo T., Griswold AJ., Forund T., Haines J., Farrer L., DeStefano A., Wijsman E., Mayeux R., Pericak-Vance M., Kunkle B., Goate A., Schellenberg GD., Vardarajan B., Wang L-S., Leung YY., Dalgard CL., Nicolas G., Wallon D., Dufouil C., Pasquier F., Hanon O., Debette S., Grünblatt E., Popp J., Angel B., Gloger S., Chacon MV., Aranguiz R., Orellana P., Slachevsky A., Gonzalez-Billault C., Albala C., Fuentes P., Sachdev P., Mather KA., Hauger RL., Merritt V., Panizzon M., Zhang R., Gaziano JM., Ghidoni R., Galimberti D., Arosio B., Mecocci P., Solfrizzi V., Parnetti L., Squassina A., Tremolizzo L., Borroni B., Nacmias B., Caffarra P., Seripa D., Rainero I., Daniele A., Piras F., EADB None., Leonard HL., Yokoyama JS., Nalls MA., Miyashita A., Hara N., Ozaki K., Niida S., Williams J., Masullo C., Amouyel P., Preux P-M., Mbelesso P., Bandzouzi B., Saykin A., Jessen F., Kehoe PG., Van Duijn C., Ben Salem N., Frikke-Schmidt R., Cherni L., Greicius MD., Tsolaki M., Sánchez-Juan P., Romano Silva MA., Porter T., Laws SM., Sleegers K., Ingelsson M., Dartigues J-F., Seshadri S., Rossi G., Morelli L., Hiltunen M., Sims R., van der Flier W., Andreassen OA., Arboleda H., Cruchaga C., Escott-Price V., Ruiz A., Lee KH., Ikeuchi T., Ramirez A., Gim J., Logue M., Lambert J-C.
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.