Transferability of a European-derived Alzheimer’s Disease Genetic Risk Score across Multi-Ancestry Populations

Author:

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

Abstract

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.

Publisher

Cold Spring Harbor Laboratory

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