Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.
Nicolas Aude, Sherva Richard, Grenier-Boley Benjamin, Kim Yoontae, Kikuchi Masataka, Timsina Jigyasha, de Rojas Itziar, Dalmasso María Carolina, Zhou Xiaopu, Le Guen Yann, Arboleda-Bustos Carlos E, Camargos Bicalho Maria Aparecida, Guerchet Maëlenn, van der Lee Sven, Goss Monica, Castillo Atahualpa, Bellenguez Céline, Küçükali Fahri, Satizabal Claudia L, 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, García-Alberca Jose María, Royo Jose Luís, Rodriguez-Rodriguez Eloy, Soininen Hilkka, Heikkinen Sami, de Mendonça Alexandre, Mehrabian Shima, Traykov Latchezar, Hort Jakub, Vyhnalek Martin, Rasmussen Katrine Laura, Thomassen Jesper Qvist, Pijnenburg Yolande A L, Holstege Henne, van Swieten John C, Seelaar Harro, Claassen Jurgen A H R, Jansen Willemijn J, Ramakers Inez, Verhey Frans, van der Lugt Aad, Scheltens Philip, Ortega-Rojas Jenny, Concha Mera Ana Gabriela, Mahecha Maria F, Pardo Rodrigo, Arboleda Gonzalo, Bahrami Shahram, Fominykh Vera, Selbæk Geir, Graff Caroline, Papenberg Goran, Giedraitis Vilmantas, Boland Anne, Deleuze Jean-François, de Marco Luiz Armando, de Moraes Edgar Nunes, de Mattos Viana Bernardo, Túlio Gualberto Cintra Marco, Juarez-Cedillo Teresa, Griswold Anthony J, Forund Tatiana, 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 L, Nicolas Gael, Wallon David, Dufouil Carole, Pasquier Florence, Hanon Olivier, Debette Stéphanie, Grünblatt Edna, Popp Julius, Angel Bárbara, Gloger Sergio, Chacon Maria Victoria, Aranguiz Rafael, Orellana Paulina, Slachevsky Andrea, Gonzalez-Billault Christian, Albala Cecilia, Fuentes Patricio, Sachdev Perminder, Mather Karen A, Hauger Richard L, Merritt Victoria, Panizzon Matthew, Zhang Rui, Gaziano J 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, EADB, Leonard Hampton L, Yokoyama Jenifer S, Nalls Mike A, 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 G, Van Duijn Cornelia, Ben Salem Nesrine, Frikke-Schmidt Ruth, Cherni Lotfi, Greicius Michael D, Tsolaki Magda, Sánchez-Juan Pascual, Romano Silva Marco Aurélio, Porter Tenielle, Laws Simon M, Sleegers Kristel, Ingelsson Martin, Dartigues Jean-François, Seshadri Sudha, Rossi Giacomina, Morelli Laura, Hiltunen Mikko, Sims Rebecca, van der Flier Wiesje, Andreassen Ole A, Arboleda Humberto, Cruchaga Carlos, Escott-Price Valentina, Ruiz Agustín, Lee Kun Ho, Ikeuchi Takeshi, Ramirez Alfredo, Gim Jungsoo, Logue Mark, Lambert Jean-Charles
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Аннотация
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.
Для цитирования: Nicolas Aude, Sherva Richard, Grenier-Boley Benjamin, Kim Yoontae, Kikuchi Masataka, Timsina Jigyasha, de Rojas Itziar, Dalmasso María Carolina, Zhou Xiaopu, Le Guen Yann, Arboleda-Bustos Carlos E, Camargos Bicalho Maria Aparecida, Guerchet Maëlenn, van der Lee Sven, Goss Monica, Castillo Atahualpa, Bellenguez Céline, Küçükali Fahri, Satizabal Claudia L, 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, García-Alberca Jose María, Royo Jose Luís, Rodriguez-Rodriguez Eloy, Soininen Hilkka, Heikkinen Sami, de Mendonça Alexandre, Mehrabian Shima, Traykov Latchezar, Hort Jakub, Vyhnalek Martin, Rasmussen Katrine Laura, Thomassen Jesper Qvist, Pijnenburg Yolande A L, Holstege Henne, van Swieten John C, Seelaar Harro, Claassen Jurgen A H R, Jansen Willemijn J, Ramakers Inez, Verhey Frans, van der Lugt Aad, Scheltens Philip, Ortega-Rojas Jenny, Concha Mera Ana Gabriela, Mahecha Maria F, Pardo Rodrigo, Arboleda Gonzalo, Bahrami Shahram, Fominykh Vera, Selbæk Geir, Graff Caroline, Papenberg Goran, Giedraitis Vilmantas, Boland Anne, Deleuze Jean-François, de Marco Luiz Armando, de Moraes Edgar Nunes, de Mattos Viana Bernardo, Túlio Gualberto Cintra Marco, Juarez-Cedillo Teresa, Griswold Anthony J, Forund Tatiana, 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 L, Nicolas Gael, Wallon David, Dufouil Carole, Pasquier Florence, Hanon Olivier, Debette Stéphanie, Grünblatt Edna, Popp Julius, Angel Bárbara, Gloger Sergio, Chacon Maria Victoria, Aranguiz Rafael, Orellana Paulina, Slachevsky Andrea, Gonzalez-Billault Christian, Albala Cecilia, Fuentes Patricio, Sachdev Perminder, Mather Karen A, Hauger Richard L, Merritt Victoria, Panizzon Matthew, Zhang Rui, Gaziano J 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, EADB, Leonard Hampton L, Yokoyama Jenifer S, Nalls Mike A, 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 G, Van Duijn Cornelia, Ben Salem Nesrine, Frikke-Schmidt Ruth, Cherni Lotfi, Greicius Michael D, Tsolaki Magda, Sánchez-Juan Pascual, Romano Silva Marco Aurélio, Porter Tenielle, Laws Simon M, Sleegers Kristel, Ingelsson Martin, Dartigues Jean-François, Seshadri Sudha, Rossi Giacomina, Morelli Laura, Hiltunen Mikko, Sims Rebecca, van der Flier Wiesje, Andreassen Ole A, Arboleda Humberto, Cruchaga Carlos, Escott-Price Valentina, Ruiz Agustín, Lee Kun Ho, Ikeuchi Takeshi, Ramirez Alfredo, Gim Jungsoo, Logue Mark, Lambert Jean-Charles. Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.. Nature genetics. 2025. DOI: 10.1038/s41588-025-02227-w.
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