Transferability of a European-derived Alzheimer’s Disease Genetic Risk Score across Multi-Ancestry Populations
Authors: Nicolas Aude , Grenier-Boley Benjamin , Sherva Richard , Kim Yoontae , Kikuchi Masataka , de Rojas Itziar , Dalmasso Carolina , Zhou Xiaopu , Guen Yann Le , Arboleda-Bustos Carlos E , Camargos Bicalho Maria Aparecida , Guerchet Maëlenn , van der Lee Sven , Goss Monica , Castillo Atahualpa , Bellenguez Céline , Küçükali Fahri , Satizabal Barrera Claudia , Fongang Bernard , yang Qiong , Peters Oliver , Schneider Anja , Dichgans Martin , Rujescu Dan , Scherbaum Norbert , Deckert Jürgen , Riedel-Heller Steffi , Hausner Lucrezia , Molina Porcel Laura , Düzel Emrah , Grimmer Timo , Wiltfang Jens , Heilmann-Heimbach Stefanie , Moebus Susanne , Tegos Thomas , Scarmeas Nikolaos , Dols-Icardo Oriol , Moreno Fermin , Pérez-Tur Jordi , Bullido María J. , Pastor Pau , Sánchez-Valle Raquel , Álvarez Victoria , Cao Han , Ip Nancy Y. , Fu Amy K. Y. , Ip Fanny C. F. , Olivar Natividad , Muchnik Carolina , Cuesta Carolina , Campanelli Lorenzo , Solis Patricia , Politis Daniel Gustavo , Kochen Silvia , Brusco Luis Ignacio , Boada Mercè , García-González Pablo , Puerta Raquel , Mir Pablo , Real Luis M , Piñol-Ripoll Gerard , María García-Alberca Jose , Luís Royo Jose , Rodriguez-Rodriguez Eloy , Soininen Hilkka , Heikkinen Sami , de Mendonça Alexandre , Mehrabian Shima , Traykov Latchezar , Hort Jakub , Vyhnalek Martin , Rasmussen Katrine Laura , Qvist Thomassen Jesper , Pijnenburg Yolande A.L. , Holstege Henne , van Swieten John , Ramakers Inez , Verhey Frans , van der Lugt Aad , Scheltens Philip , Ortega-Rojas Jenny , Concha Mera Ana Gabriela , Mahecha Maria F. , Pardo Rodrogo , Arboleda Gonzalo , Graff Caroline , Papenberg Goran , Giedraitis Vilmantas , Boland Anne , Deleuze Jean-François , Armando de Marco Luiz , Nunes de Moraes Edgar , de Viana Bernardo , Túlio Gualberto Cintra Marco , Grsiwold Anthony , Forund Tatiana , Cruchaga Carlos , Haines Jonathan , Farrer Lindsay , DeStefano Anita , Wijsman Ellen , Mayeux Richard , Pericak-Vance Margaret , Kunkle Brian , Goate Alison , Schellenberg Gerard D. , Vardarajan Badri , Wang Li-San , Leung Yuk Yee , Dalgard Clifton , Nicolas Gael , Wallon David , Dufouil Carole , Pasquier Florence , Hanon Olivier , Debette Stéphanie , Grünblatt Edna , Popp Julius , Angel Bárbara , Golger Sergio , Victoria Chacon Maria , Aranguiz Rafael , Orellana Paulina , Slachevsky Andrea , Gonzalez-Billault Christian , Albala Cecilia , Fuentes Patricio , Porter Tenielle , Laws Simon M , Sachdev Perminder , Mather Karen , Hauger Richard L. , Merritt Victoria , Panizzon Matthew , Zhang Rui , Gaziano Michael , Ghidoni Roberta , Galimberti Daniela , Arosio Beatrice , Mecocci Patrizia , Solfrizzi Vincenzo , Parnetti Lucilla , Squassina Alessio , Tremolizzo Lucio , Borroni Barbara , Nacmias Benedetta , Caffarra Paolo , Seripa Davide , Rainero Innocenzo , Daniele Antonio , Piras Fabrizio , Miyashita Akinori , Hara Norikazu , Ozaki Kouichi , Niida Shumpei , Williams Julie , Masullo Carlo , Amouyel Philippe , Preux Pierre-Marie , Mbelesso Pascal , Bandzouzi Bébène , Saykin Andy , Jessen Frank , Kehoe Patrick , Van Duijn Cornelia , Gim Jungsoo , Ben Salem Nesrine , Frikke-Schmidt Ruth , Cherni Lofti , Greicius Michael D. , Tsolaki Magda , Sánchez-Juan Pascual , Romano Silva Marco Aurélio , Sleegers Kristel , Ingelsson Martin , Dartigues Jean-François , Seshadri Sudha , Rossi Giacomina , Morelli Laura , Hiltunen Mikko , Sims Rebecca , van der Flier Wiesje , Andreassen Ole , Arboleda Humberto , Escott-Price Valentina , Ruiz Agustín , Lee Kun Ho , Ikeuchi Takeshi , Ramirez Alfredo , Logue Mark , Lambert Jean-Charles 
Published: October 2023

We built a genetic risk score (GRS) from the most complete landscape of the Alzheimer disease (AD) genetics. We extended its analysis in 16 European countries and observed a consistent association of this GRS with AD risk, age at onset and cerebrospinal fluid (CSF) AD biomarker levels regardless of theApolipoprotein E (APOE)genotype. This GRS was also associated with AD risk (independently ofAPOE) with a decreasing order of magnitude in those with an European-American, North-African, East-Asian, Latin-American, African-American background respectively. No association of the GRS to AD was seen in sub-Saharan African and Indian populations. This GRS captures information specific to AD as its association decreases as the diagnosis broadens. In conclusion, a simple GRS captures shared genetic information specific to AD between multi-ancestry populations. However, more population diversity is needed to better understand the AD genetic complexity across populations.