Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations

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 cerebrospina...

Full description

Bibliographic Details
Authors: Nicolas, Aude, Sherva, Richard|||0000-0003-2133-1493, Grenier-Boley, Benjamin, Kim, Yoontae, Kikuchi, Masataka|||0000-0002-9562-841X, Timsina, Jigyasha, De Rojas, Itziar|||0000-0002-2148-381X, Dalmasso, Maria Carolina|||0000-0002-4901-9955, Le Guen, Yann|||0000-0001-6649-8364, Guerchet, Maëlenn|||0000-0002-0470-5556, van der Lee, Sven J.|||0000-0003-1606-8643, Castillo, Atahualpa, Bellenguez, Céline|||0000-0002-1240-7874, Küçükali, Fahri, Satizabal, Claudia L.|||0000-0002-1115-4430, Yang, Qiong|||0000-0002-3658-1375, Peters, Oliver|||0000-0003-0568-2998, Schneider, Anja|||0000-0001-9540-8700, Dichgans, Martin|||0000-0002-0654-387X, Rujescu, Dan|||0000-0002-1432-313X, Scherbaum, Norbert|||0000-0003-1759-6990, Deckert, Jürgen|||0000-0003-1008-4650, Riedel-Heller, Steffi|||0000-0003-4321-6090, Hausner, Lucrezia|||0000-0001-9009-2356, Molina-Porcel, Laura|||0000-0003-4068-8578, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie|||0000-0003-1057-465X, Moebus, Susanne|||0000-0002-0072-5410, Tegos, Thomas, Scarmeas, Nikolaos|||0000-0001-6453-8908, Dols Icardo, Oriol|||0000-0003-2656-8748, Moreno, Fermin|||0000-0001-5200-3164, Pérez-Tur, Jordi|||0000-0002-9111-1712, Bullido, María J.|||0000-0002-6477-1117, Pastor, Pau|||0000-0002-7493-8777, Sanchez-Valle, Raquel|||0000-0001-7750-896X, Alvarez, Victoria|||0000-0002-1916-2523, Cao, Han|||0000-0001-9992-9108, Ip, Nancy Y.|||0000-0002-2763-8907, Fu, Amy K.Y.|||0000-0003-4085-6201, Olivar, Natividad, Muchnik, Carolina, Solis, Patricia, Brusco, Luis Ignacio, Boada, Mercè|||0000-0003-2617-3009, García-González, Pablo|||0000-0003-0125-5403, Puerta, Raquel|||0000-0002-1191-5893, Mir, Pablo|||0000-0003-1656-302X, Real, Luis M.|||0000-0003-4932-7429, Piñol-Ripoll, Gerard, García-Alberca, Jose Maria, Royo, Jose Luís, Rodríguez-Rodríguez, Eloy|||0000-0001-7742-677X, Soininen, Hilkka|||0000-0002-2785-9937, Heikkinen, Sami|||0000-0002-6083-2402, de Mendonça, Alexandre|||0000-0002-0488-1453, Mehrabian, Shima|||0000-0002-3146-6001, Traykov, Latchezar, Hort, Jakub|||0000-0002-1080-3726, Vyhnalek, Martin, Rasmussen, Katrine Laura, Thomassen, Jesper Qvist|||0000-0003-3484-9531, Pijnenburg, Yolande A.L., Holstege, Henne|||0000-0002-7688-3087, van Swieten, John C., Seelaar, Harro|||0000-0003-1989-7527, Claassen, Jurgen A. H. R., Jansen, Willemijn J., Ramakers, Inez, Verhey, Frans, van der Lugt, Aad, Scheltens, Philip|||0000-0002-1046-6408, Mahecha, Maria F.|||0000-0002-2306-5216, Bahrami, Shahram, Fominykh, Vera|||0000-0001-5490-2390, Selbæk, Geir|||0000-0001-6511-8219, Graff, Caroline|||0000-0002-9949-2951, Papenberg, Goran, Giedraitis, Vilmantas|||0000-0003-3423-2021, Boland, Anne|||0000-0001-8789-5676, Deleuze, Jean François, Juarez-Cedillo, Teresa|||0000-0002-9442-3471, Haines, Jonathan L.|||0000-0002-4351-4728, Farrer, Lindsay A.|||0000-0001-5533-4225, DeStefano, Anita, Mayeux, Richard|||0000-0001-6519-9696, Pericak-Vance, Margaret, Kunkle, Brian, Goate, Alison|||0000-0002-0576-2472, Schellenberg, Gerard D., Leung, Yuk Yee|||0000-0002-3047-5440, Dalgard, Clifton L.|||0000-0003-2025-8239, Nicolas, Gael|||0000-0001-9391-7800, Wallon, David|||0000-0002-2634-7198, Dufouil, Carole|||0000-0003-2442-4476, Pasquier, Florence|||0000-0001-9880-9788, Hanon, Olivier|||0000-0002-4697-122X, Debette, Stéphanie|||0000-0001-8675-7968, Grünblatt, Edna|||0000-0001-8505-7265, Popp, Julius|||0000-0002-0068-0312, Slachevsky, Andrea, Gonzalez-Billault, Christian, Albala, Cecilia, Sachdev, Perminder S.|||0000-0002-9595-3220, Mather, Karen A.|||0000-0003-4143-8941, Zhang, Rui|||0000-0002-7235-505X, Gaziano, J. Michael, Ghidoni, Roberta|||0000-0002-7691-1957, Galimberti, Daniela|||0000-0002-9284-5953, Arosio, Beatrice|||0000-0002-0615-3580, Mecocci, Patrizia|||0000-0003-0729-5246, Solfrizzi, Vincenzo|||0000-0002-8524-0315, Parnetti, Lucilla|||0000-0001-5722-3967, Squassina, Alessio|||0000-0001-7415-7607, Tremolizzo, Lucio|||0000-0003-0473-6560, Borroni, Barbara|||0000-0001-9340-9814, Nacmias, Benedetta|||0000-0001-9338-9040, Caffarra, Paolo, Seripa, Davide|||0000-0001-7331-0470, Rainero, Innocenzo|||0000-0001-6074-9628, Daniele, Antonio|||0000-0003-1641-5852, Piras, Fabrizio|||0000-0003-3566-5494, Zulaica, Miren, Yannakoulia, Mary, Weinhold, Leonie, Wagner, Michael, Vogelgsang, Jonathan|||0000-0001-9326-8193, Vandenberghe, Rik|||0000-0001-6237-2502, Van Dongen, Jasper|||0000-0001-5599-0046, Van Broeckhoven, Christine|||0000-0003-0183-7665, Valero, Sergi|||0000-0002-6599-948X, Ullgren, Abbe, Tybjærg-Hansen, Anne, Thalamuthu, Anbupalam|||0000-0002-7114-1260, Tesí, Niccolo, Tárraga, Lluís|||0000-0002-8423-946X, Stordal, Eystein|||0000-0002-2443-7923, Spottke, Annika, Sotolongo Grau, Oscar|||0000-0002-9679-0670, Sorbi, Sandro|||0000-0002-0380-6670, Schott, Jonathan M.|||0000-0003-2059-024X, Schmid, Matthias, Scherer, Martin, Scarpini, Elio|||0000-0002-6395-2119, Scamosci, Michela, Sando, Sigrid B., Sánchez-Juan, Pascual|||0000-0002-6081-8037, Sánchez García, Florentino, Bernal Sánchez-Arjona, María, Sanabria, Ángela|||0000-0002-7501-9895, Saltvedt, Ingvild|||0000-0002-7897-9808, Sakka, Paraskevi, Sáez, María Eugenia|||0000-0001-9299-2534, Rubino, Elisa|||0000-0002-7553-7553, Royo, Jose Luis|||0000-0003-2024-4363, Rosende-Roca, Maitée|||0000-0003-1778-8175, Rongve, Arvid|||0000-0002-0476-4134, Roberto Herrero, Natalia|||0000-0002-5391-2711, Riederer, Peter, Rábano, Alberto|||0000-0001-9320-6566, Quintela, Inés|||0000-0002-0239-7975, Quenez, Olivier|||0000-0002-8273-8505, Priller, Josef|||0000-0001-7596-0979, Posthuma, Danielle|||0000-0001-7582-2365, Polak, Thomas, Pisanu, Claudia|||0000-0002-9151-4319, Pineda, Juan A.|||0000-0002-3751-0296, Pérez-Cordón, Alba|||0000-0002-6028-0791, Padovani, Alessandro|||0000-0002-0119-3639, Ortega, Gemma, Orellana del Río, Adelina|||0000-0002-0204-1944, Nordestgaard, Børge G.|||0000-0002-1954-7220, Ngandu, Tiia, Morgan, Kevin|||0000-0002-8217-2396, Montrreal Navarro, Laura|||0000-0002-0010-645X, Mendez-Gonzalez, Manuel|||0000-0002-5218-0774, Mendoza, Silvia, Meggy, Alun, Medina, Miguel|||0000-0002-7016-5340, Mead, Simon|||0000-0002-4326-1468, Martínez Rodríguez, Carmen, Marshall, Rachel, Marquié, Marta|||0000-0002-0660-0950, Spallazzi, Marco|||0000-0002-8091-2063, Mangialasche, Francesca, Maier, Wolfgang, Macías, Juan|||0000-0002-4778-790X, Luckcuck, Lauren, Love, Seth, López-de Munain, Adolfo, Lleó, Alberto|||0000-0002-2568-5478, Lerch, Ondrej, Lehtisalo, Jenni, Lage, Carmen|||0000-0003-1703-121X, Kosmidis, Mary H., Kornhuber, Johannes|||0000-0002-8096-3987, Kivipelto, Miia, Kilander, Lena, Biessels, Geert Jan|||0000-0001-6862-2496, Hulsman, Marc|||0000-0002-9889-3606, Huerto Vilas, Raquel, Holmes, Clive, Hoffmann, Per|||0000-0002-6573-983X, Herrmann, Martin J.|||0000-0001-9970-2122, Hernández, Isabel|||0000-0001-8119-393X, Heneka, Michael|||0000-0003-4996-1630, Helisalmi, Seppo, Hartmann, Annette M., Hardy, John|||0000-0002-3122-0423, Hampel, Harald, Hadjigeorgiou, Georgios, Haapasalo, Annakaisa|||0000-0003-0959-2957, Grande, Giulia, González-Pérez, Antonio, Goldhardt, Oliver, Giegling, Ina, García-Ribas, Guillermo, Froelich, Lutz|||0000-0003-1494-0813, Frank-García, Ana, Fox, Nick C.|||0000-0002-6660-657X, Fostinelli, Silvia, Foroud, Tatiana M., Fortea, Juan|||0000-0002-1340-638X, Fließbach, Klaus, Fladby, Tormod|||0000-0002-9984-9797, Fischer, Peter, Ferri, Evelyn, Ferreira, Catarina B., Fernández-Fuertes, Marta, Fenoglio, Chiara|||0000-0001-6332-4721, Farotti, Lucia, Nielsen, Sune Fallgaard, Ewers, Michael|||0000-0001-5231-1714, Espinosa, Ana|||0000-0001-7399-3267, Engelborghs, Sebastiaan|||0000-0003-0304-9785, Duron, Emmanuelle, Djurovic, Srdjan|||0000-0002-8140-8061, Diez-Fairen, Monica|||0000-0003-1882-0309, Diehl-Schmid, Janine|||0000-0002-7745-1382, Denning, Nicola|||0000-0001-8467-7382, del Ser, Teodoro|||0000-0001-9806-7083, De Deyn, Peter Paul|||0000-0002-2228-2964, Dardiotis, Efthimios|||0000-0003-2957-641X, Daian, Delphine, Custodero, Carlo|||0000-0003-1549-6451, Conti, Elisa, Clark, Christopher|||0000-0001-7210-7702, Clarimón, Jordi|||0000-0002-6824-6942, Ciccone, Simona, Chillotti, Caterina, Charbonnier, Camille|||0000-0003-1172-0196, Cervera Carles, Laura|||0000-0003-2286-200X, Cecchetti, Roberta, Carracedo, Ángel|||0000-0003-1085-8986, Chene, Geneviève|||0000-0002-8368-6460, Calero, Miguel|||0000-0001-5366-3324, Burholt, Vanessa|||0000-0002-6789-127X, Bûrger, Katharina, Buiza-Rueda, Dolores|||0000-0002-3504-9299, Brookes, Keeley J.|||0000-0003-2427-2513, Brodaty, Henry|||0000-0001-9487-6617, Bresner, Catherine|||0000-0003-2673-9762, Bråthen, Geir|||0000-0003-3224-7983, Bossù, Paola|||0000-0002-1432-0078, Boschi, Silvia|||0000-0003-1610-1917, Blesa, Rafael|||0000-0003-4026-2884, Bizarro, Alessandra, Binetti, Giuliano|||0000-0003-2759-5844, Bessi, Valentina|||0000-0002-6176-3584, Besse, Céline, Berr, Claudine|||0000-0001-5254-7655, Bellini, Sonia|||0000-0002-6162-252X, Pastor, Ana Belén|||0000-0001-9637-4688, Baquero, Miquel|||0000-0002-6861-1831, Banaj, Nerisa|||0000-0002-6317-8549, Bailly, Henri, Athanasiu, Lavinia, Arias Pastor, Alfonso, Archetti, Silvana, Arcaro, Marina|||0000-0002-3821-0682, Appollonio, Ildebrando, Armstrong, Nicola|||0000-0002-4477-293X, Alvarez, Ignacio|||0000-0002-8537-3935, Alegret, Montserrat|||0000-0002-8164-9500, Alcolea, Daniel|||0000-0002-3819-3245, Alarcón-Martín, Emilio|||0000-0002-0985-872X, Abdelnour, Carla|||0000-0002-7636-9758, Aarsland, Dag|||0000-0001-6314-216X, Kleineidam, Luca, Holmans, Peter|||0000-0003-0870-9412, Amin, Najaf|||0000-0002-8944-1771, Moreno-Grau, Sonia, Leonard, Hampton L.|||0000-0003-2390-8110, Nalls, Mike A., Miyashita, Akinori, Hara, Norikazu|||0000-0001-8525-3469, Ozaki, Kouichi|||0000-0003-0028-1570, Williams, Julie|||0000-0002-4069-0259, Masullo, Carlo|||0000-0001-7798-3410, Amouyel, Philippe|||0000-0001-9088-234X, Jessen, Frank, Kehoe, Patrick|||0000-0002-7542-1139, van Duijn, Cornelia M.|||0000-0002-2374-9204, Frikke-Schmidt, Ruth|||0000-0003-4084-5027, Greicius, Michael D., Tsolaki, Magda|||0000-0002-2072-8010, Laws, Simon M., Sleegers, Kristel|||0000-0002-0283-2332, Ingelsson, Martin|||0000-0001-5466-8370, Seshadri, Sudha|||0000-0001-6135-2622, Rossi, Giacomina|||0000-0001-6680-2725, Morelli, Laura, Hiltunen, Mikko|||0000-0003-3566-4096, Sims, Rebecca|||0000-0002-3885-1199, van der Flier, Wiesje M.|||0000-0001-8766-6224, Andreassen, Ole A.|||0000-0002-4461-3568, Cruchaga, Carlos|||0000-0002-0276-2899, Escott-Price, Valentina|||0000-0003-1784-5483, Ruiz Laza, Agustín|||0000-0003-2633-2495, Lee, Kun Ho, Ikeuchi, Takeshi|||0000-0001-8828-8085, Ramirez, Alfredo|||0000-0003-4991-763X, Gim, Jungsoo|||0000-0002-6454-9751, Lambert, Jean-Charles|||0000-0003-0829-7817, Zhou, Xiaopu, Arboleda-Bustos, Carlos E., Bicalho, Maria Aparecida Camargos, Goss, Monica, Fongang, Bernard, Ip, Fanny C.F., Cuesta, Carolina, Campanelli, Lorenzo, Gustavo Politis, Daniel, Kochen, Silvia, Ortega-Rojas, Jenny, Concha Mera, Ana Gabriela, Pardo, Rodrigo, Arboleda, Gonzalo, de Marco, Luiz Armando, Nunes de Moraes, Edgar, de Mattos Viana, Bernardo, Túlio Gualberto Cintra, Marco, Griswold, Anthony J., Forund, Tatiana, Wijsman, Ellen, Vardarajan, Badri N., Wang, Li-San, Angel, Bárbara, Gloger, Sergio, VictoriaChacon, Maria, Aranguiz, Rafael, Orellana, Paulina, Fuentes, Patricio, Hauger, Richard L., Merritt, Victoria, Panizzon, Matthew, Woods, Bob, Vidal, Jean-Sébastien|||0000-0001-6770-0720, Ulstein, Ingun D., Uitterlinden, André G.|||0000-0002-7276-3387, Tartan, Juan Pablo, Solomon, Alina, Skrobot, Olivia Anna, Shadrin, Alexey A., Rosas Allende, Irene, Reinders, Marcel J. T.|||0000-0002-1148-1562, Pericard, Pierre, Orsini, Michela, Olaso, Robert, Möthen, Markus M., Mol, Merel O.|||0000-0003-2533-2530, Martín Montes, Angel|||0000-0002-1694-786X, MacLeod, Catherine A., Löwemark, Malin, Lauria, Alessandra, Laukka, Erika J., Koivisto, Anne, Kinhult Ståhlbom, Anne, Johansson, Charlotte, Harwood, Janet, Guetta-Baranes, Tamar, Green, Emma, Giaccone, Giorgio|||0000-0002-4803-0802, García-Madrona, Sebastián, Franco-Macías, Emilio|||0000-0003-4186-1037, Fin, Bertrand, Tagliavini, Fabrizio|||0000-0003-1039-7315, Dionigi Rossi, Paolo, Giuffrè, Guido Maria, Corma Gómez, Anaïs|||0000-0002-1078-0237, Tsolaki, Anthoula|||0000-0002-5563-7776, Yokoyama, Jenifer S., Niida, Shumpei, Preux, Pierre Marie, Mbelesso, Pascal, Bandzouzi, Bébène, Saykin, Andy, Ben Salem, Nesrine, Cherni, Lotfi, Romano Silva, Marco Aurélio, Porter, Tenielle, Dartigues, Jean-François, Arboleda, Humberto, Logue, Mark W.
Format: article
Publication Date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:325972
Online Access:https://ddd.uab.cat/record/325972
https://dx.doi.org/urn:doi:10.1038/s41588-025-02227-w
Access Level:Open access
Keyword:Aged
Alzheimer Disease
Apolipoproteins E
Biomarkers
Europe
Female
Genetic Predisposition to Disease
Genetic Risk Score
Genome-Wide Association Study
Humans
Male
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Factors
White People
Description
Summary: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.