Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all...

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Detalhes bibliográficos
Autores: De Rojas, Itziar|||0000-0002-2148-381X, Moreno-Grau, Sonia, Tesi, Niccolo|||0000-0002-1413-5091, Grenier-Boley, Benjamin, Andrade, Victor|||0000-0003-0682-269X, Jansen, Iris E.|||0000-0003-1901-8131, Pedersen, Nancy L.|||0000-0001-8057-3543, Stringa, Najada|||0000-0001-6350-452X, Zettergren, Anna|||0000-0002-7182-8417, Hernández, Isabel|||0000-0001-8119-393X, Montrreal Navarro, Laura|||0000-0002-0010-645X, Antúnez, Carmen, Antonell, Anna|||0000-0002-3286-8459, Tankard, Rick M.|||0000-0002-8847-9401, Bis, Joshua C.|||0000-0002-3409-1110, Sims, Rebecca|||0000-0002-3885-1199, Bellenguez, Céline|||0000-0002-1240-7874, Quintela, Inés|||0000-0002-0239-7975, González-Perez, Antonio, Calero, Miguel|||0000-0001-5366-3324, Franco-Macías, Emilio|||0000-0003-4186-1037, Macías, Juan|||0000-0002-4778-790X, Blesa, Rafael|||0000-0003-4026-2884, Cervera Carles, Laura|||0000-0003-2286-200X, Mendez-Gonzalez, Manuel|||0000-0002-5218-0774, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin|||0000-0001-5200-3164, Huerto Vilas, Raquel, Baquero, Miquel|||0000-0002-6861-1831, Diez-Fairen, Monica|||0000-0003-1882-0309, Lage, Carmen|||0000-0003-1703-121X, García-Madrona, Sebastián, García-González, Pablo|||0000-0003-0125-5403, Alarcón-Martín, Emilio|||0000-0002-0985-872X, Valero, Sergi|||0000-0002-6599-948X, Sotolongo Grau, Oscar|||0000-0002-9679-0670, Ullgren, Abbe, Naj, Adam C.|||0000-0002-9621-2942, Lemstra, Afina W.|||0000-0002-8933-3260, Benaque, Alba, Pérez-Cordón, Alba|||0000-0002-6028-0791, Benussi, Alberto|||0000-0002-8703-6940, Rábano, Alberto|||0000-0001-9320-6566, Padovani, Alessandro|||0000-0002-0119-3639, Squassina, Alessio|||0000-0001-7415-7607, de Mendonça, Alexandre|||0000-0002-0488-1453, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén|||0000-0001-9637-4688, Espinosa, Ana|||0000-0001-7399-3267, Corma Gómez, Anaïs|||0000-0002-1078-0237, Martín Montes, Angel|||0000-0002-1694-786X, Sanabria, Ángela|||0000-0002-7501-9895, DeStefano, Anita L.|||0000-0002-9335-2819, Schneider, Anja|||0000-0001-9540-8700, Haapasalo, Annakaisa|||0000-0003-0959-2957, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid|||0000-0002-0476-4134, Borroni, Barbara|||0000-0001-9340-9814, Arosio, Beatrice|||0000-0002-0615-3580, Nacmias, Benedetta|||0000-0001-9338-9040, Nordestgaard, Børge G.|||0000-0002-1954-7220, Kunkle, Brian W., Charbonnier, Camille|||0000-0003-1172-0196, Abdelnour, Carla|||0000-0002-7636-9758, Masullo, Carlo|||0000-0001-7798-3410, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole|||0000-0003-2442-4476, Graff, Caroline|||0000-0002-9949-2951, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A.|||0000-0001-6502-7173, Fenoglio, Chiara|||0000-0001-6332-4721, Van Broeckhoven, Christine|||0000-0003-0183-7665, Clark, Christopher|||0000-0001-7210-7702, Pisanu, Claudia|||0000-0002-9151-4319, Satizabal, Claudia L.|||0000-0002-1115-4430, Holmes, Clive, Buiza-Rueda, Dolores|||0000-0002-3504-9299, Aarsland, Dag|||0000-0001-6314-216X, Rujescu, Dan|||0000-0002-1432-313X, Alcolea, Daniel|||0000-0002-3819-3245, Galimberti, Daniela|||0000-0002-9284-5953, Wallon, David|||0000-0002-2634-7198, Seripa, Davide|||0000-0001-7331-0470, Grünblatt, Edna|||0000-0001-8505-7265, Dardiotis, Efthimios|||0000-0003-2957-641X, Düzel, Emrah, Scarpini, Elio|||0000-0002-6395-2119, Conti, Elisa, Rubino, Elisa|||0000-0002-7553-7553, Gelpi, Ellen|||0000-0003-2948-4187, Rodríguez-Rodríguez, Eloy|||0000-0001-7742-677X, Duron, Emmanuelle, Boerwinkle, Eric|||0000-0001-8813-0544, Ferri, Evelyn, Tagliavini, Fabrizio|||0000-0003-1039-7315, Küçükali, Fahri, Pasquier, Florence|||0000-0001-9880-9788, Sánchez García, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gael|||0000-0001-9391-7800, Selbæk, Geir|||0000-0001-6511-8219, Ortega Linares, Gemma|||0000-0002-7479-4072, Chene, Geneviève|||0000-0002-8368-6460, Hadjigeorgiou, Georgios, Rossi, Giacomina|||0000-0001-6680-2725, Spalletta, Gianfranco|||0000-0002-7432-4249, Giaccone, Giorgio|||0000-0002-4803-0802, Grande, Giulia, Binetti, Giuliano|||0000-0003-2759-5844, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik|||0000-0003-3930-4354, Soininen, Hilkka|||0000-0002-2785-9937, Karlsson, Ida K., Alvarez, Ignacio|||0000-0002-8537-3935, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild|||0000-0002-7897-9808, Rainero, Innocenzo|||0000-0001-6074-9628, Rosas Allende, Irene, Hort, Jakub|||0000-0002-1080-3726, Diehl-Schmid, Janine|||0000-0002-7745-1382, Van Dongen, Jasper|||0000-0001-5599-0046, Vidal, Jean-Sébastien|||0000-0001-6770-0720, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist|||0000-0003-3484-9531, Kornhuber, Johannes|||0000-0002-8096-3987, Haines, Jonathan L.|||0000-0002-4351-4728, Vogelgsang, Jonathan|||0000-0001-9326-8193, Pineda, Juan A.|||0000-0002-3751-0296, Fortea, Juan|||0000-0002-1340-638X, Popp, Julius|||0000-0002-0068-0312, Deckert, Jürgen|||0000-0003-1008-4650, Buerger, Katharina, Morgan, Kevin|||0000-0002-8217-2396, Fließbach, Klaus, Sleegers, Kristel|||0000-0002-0283-2332, Molina-Porcel, Laura|||0000-0003-4068-8578, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A.|||0000-0001-5533-4225, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla|||0000-0001-5722-3967, Tremolizzo, Lucio|||0000-0003-0473-6560, Hausner, Lucrezia|||0000-0001-9009-2356, Benussi, Luisa|||0000-0003-2836-8141, Froelich, Lutz|||0000-0003-1494-0813, Ikram, M. Arfan|||0000-0003-0372-8585, Deniz Naranjo, M. 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Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:255696
Acesso em linha:https://ddd.uab.cat/record/255696
https://dx.doi.org/urn:doi:10.1038/s41467-021-22491-8
Access Level:acceso abierto
Palavra-chave:Genomics
Cognitive ageing
Risk factors
Descrição
Resumo:Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer's disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer's disease polygenic risk score.