2026-06-14T03:54:29Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/151242025-05-07T09:07:33Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud author Bellenguez, Céline author Küçükali, Fahri author Jansen, Iris E author Kleineidam, Luca author Moreno-Grau, Sonia author Amin, Najaf author Naj, Adam C author Campos-Martin, Rafael author Grenier-Boley, Benjamin author Andrade, Victor author Holmans, Peter A author Boland, Anne author Damotte, Vincent author van der Lee, Sven J author Costa, Marcos R author Kuulasmaa, Teemu author Yang, Qiong author de Rojas, Itziar author Bis, Joshua C author Yaqub, Amber author Prokic, Ivana author Chapuis, Julien author Ahmad, Shahzad author Giedraitis, Vilmantas author Aarsland, Dag author García-González, Pablo author Abdelnour, Carla author Alarcón-Martín, Emilio author Alcolea, Daniel author Alegret, Montserrat author Alvarez, Ignacio author Álvarez, Victoria author Armstrong, Nicola J author Tsolaki, Anthoula author Antúnez, Carmen author Appollonio, Ildebrando author Arcaro, Marina author Archetti, Silvana author Arias Pastor, Alfonso author Arosio, Beatrice author Athanasiu, Lavinia author Bailly, Henri author Banaj, Nerisa author Baquero, Miquel author Barral, Sandra author Beiser, Alexa author Pastor, Ana Belén author Below, Jennifer E author Benchek, Penelope author Benussi, Luisa author Berr, Claudine author Besse, Céline author Bessi, Valentina author Binetti, Giuliano author Bizarro, Alessandra author Blesa, Rafael author Boada, Mercè author Boerwinkle, Eric author Borroni, Barbara author Boschi, Silvia author Bossù, Paola author Bråthen, Geir author Bressler, Jan author Bresner, Catherine author Brodaty, Henry author Brookes, Keeley J author Brusco, Luis Ignacio author Buiza-Rueda, Dolores author Bûrger, Katharina author Burholt, Vanessa author Bush, William S author Calero, Miguel author Cantwell, Laura B author Chêne, Geneviève author Chung, Jaeyoon author Cuccaro, Michael L author Carracedo, Ángel author Cecchetti, Roberta author Cervera-Carles, Laura author Charbonnier, Camille author Chen, Hung-Hsin author Chillotti, Caterina author Ciccone, Simona author Claassen, Jurgen A H R author Clark, Christopher author Conti, Elisa author Corma-Gómez, Anaïs author Costantini, Emanuele author Custodero, Carlo author Daian, Delphine author Dalmasso, Maria Carolina author Daniele, Antonio author Dardiotis, Efthimios author Dartigues, Jean-François author de Deyn, Peter Paul author de Paiva Lopes, Katia author de Witte, Lot D author Debette, Stéphanie author Deckert, Jürgen author Del Ser, Teodoro author Denning, Nicola author DeStefano, Anita author Dichgans, Martin author Diehl-Schmid, Janine author Diez-Fairen, Mónica author Dionigi Rossi, Paolo author Djurovic, Srdjan author Duron, Emmanuelle author Düzel, Emrah author Dufouil, Carole author Eiriksdottir, Gudny author Engelborghs, Sebastiaan author Escott-Price, Valentina author Espinosa, Ana author Ewers, Michael author Faber, Kelley M author Fabrizio, Tagliavini author Fallgaard Nielsen, Sune author Fardo, David W author Farotti, Lucia author Fenoglio, Chiara author Fernández-Fuertes, Marta author Ferrari, Raffaele author Ferreira, Catarina B author Ferri, Evelyn author Fin, Bertrand author Fischer, Peter author Fladby, Tormod author Fließbach, Klaus author Fongang, Bernard author Fornage, Myriam author Fortea, Juan author Foroud, Tatiana M author Fostinelli, Silvia author Fox, Nick C author Franco-Macías, Emilio author Bullido, María Jesús author Frank-García, Ana author Froelich, Lutz author Fulton-Howard, Brian author Galimberti, Daniela author García-Alberca, Jose María author García-González, Pablo author Garcia-Madrona, Sebastian author Garcia-Ribas, Guillermo author Ghidoni, Roberta author Giegling, Ina author Giorgio, Giaccone author Goate, Alison M author Goldhardt, Oliver author Gomez-Fonseca, Duber author González-Pérez, Antonio author Graff, Caroline author Grande, Giulia author Green, Emma author Grimmer, Timo author Grünblatt, Edna author Grunin, Michelle author Gudnason, Vilmundur author Guetta-Baranes, Tamar author Haapasalo, Annakaisa author Hadjigeorgiou, Georgios author Haines, Jonathan L author Hamilton-Nelson, Kara L author Hampel, Harald author Hanon, Olivier author Hardy, John author Hartmann, Annette M author Hausner, Lucrezia author Harwood, Janet author Heilmann-Heimbach, Stefanie author Helisalmi, Seppo author Heneka, Michael T author Hernández, Isabel author Herrmann, Martin J author Hoffmann, Per author Holmes, Clive author Holstege, Henne author Vilas, Raquel Huerto author Hulsman, Marc author Humphrey, Jack author Biessels, Geert Jan author Jian, Xueqiu author Johansson, Charlotte author Jun, Gyungah R author Kastumata, Yuriko author Kauwe, John author Kehoe, Patrick G author Kilander, Lena author Ståhlbom, Anne Kinhult author Kivipelto, Miia author Koivisto, Anne author Kornhuber, Johannes author Kosmidis, Mary H author Kukull, Walter A author Kuksa, Pavel P author Kunkle, Brian W author Kuzma, Amanda B author Lage, Carmen author Laukka, Erika J author Launer, Lenore author Lauria, Alessandra author Lee, Chien-Yueh author Lehtisalo, Jenni author Lerch, Ondrej author Lleó, Alberto author Longstreth, William author Lopez, Oscar author Lopez de Munain, Adolfo author Love, Seth author Löwemark, Malin author Luckcuck, Lauren author Lunetta, Kathryn L author Ma, Yiyi author Macías, Juan author MacLeod, Catherine A author Maier, Wolfgang author Mangialasche, Francesca author Spallazzi, Marco author Marquié, Marta author Marshall, Rachel author Martin, Eden R author Martín Montes, Angel author Martínez Rodríguez, Carmen author Masullo, Carlo author Mayeux, Richard author Mead, Simon author Mecocci, Patrizia author Medina, Miguel author Meggy, Alun author Mehrabian, Shima author Mendoza, Silvia author Menéndez-González, Manuel author Mir, Pablo author Moebus, Susanne author Mol, Merel author Molina-Porcel, Laura author Montrreal, Laura author Morelli, Laura author Moreno, Fermin author Morgan, Kevin author Mosley, Thomas author Nöthen, Markus M author Muchnik, Carolina author Mukherjee, Shubhabrata author Nacmias, Benedetta author Ngandu, Tiia author Nicolas, Gael author Nordestgaard, Børge G author Olaso, Robert author Orellana, Adelina author Orsini, Michela author Ortega, Gemma author Padovani, Alessandro author Paolo, Caffarra author Papenberg, Goran author Parnetti, Lucilla author Pasquier, Florence author Pastor, Pau author Peloso, Gina author Pérez-Cordón, Alba author Pérez-Tur, Jordi author Pericard, Pierre author Peters, Oliver author Pijnenburg, Yolande A L author Pineda, Juan A author Piñol-Ripoll, Gerard author Pisanu, Claudia author Polak, Thomas author Popp, Julius author Posthuma, Danielle author Priller, Josef author Puerta, Raquel author Quenez, Olivier author Quintela, Inés author Thomassen, Jesper Qvist author Rábano, Alberto author Rainero, Innocenzo author Rajabli, Farid author Ramakers, Inez author Real, Luis M author Reinders, Marcel J T author Reitz, Christiane author Reyes-Dumeyer, Dolly author Ridge, Perry author Riedel-Heller, Steffi author Riederer, Peter author Roberto, Natalia author Rodriguez-Rodriguez, Eloy author Rongve, Arvid author Allende, Irene Rosas author Rosende-Roca, Maitée author Royo, José Luis author Rubino, Elisa author Rujescu, Dan author Sáez, María Eugenia author Sakka, Paraskevi author Saltvedt, Ingvild author Sanabria, Ángela author Sánchez-Arjona, María Bernal author Sanchez-Garcia, Florentino author Pascual Sánchez, Juan author Sánchez-Valle, Raquel author Sando, Sigrid B author Sarnowski, Chloé author Satizabal, Claudia L author Scamosci, Michela author Scarmeas, Nikolaos author Scarpini, Elio author Scheltens, Philip author Scherbaum, Norbert author Scherer, Martin author Schmid, Matthias author Schneider, Anja author Schott, Jonathan M author Selbæk, Geir author Seripa, Davide author Serrano, Manuel author Sha, Jin author Shadrin, Alexey A author Skrobot, Olivia author Slifer, Susan author Snijders, Gijsje J L author Soininen, Hilkka author Solfrizzi, Vincenzo author Solomon, Alina author Song, Yeunjoo author Sorbi, Sandro author Sotolongo-Grau, Oscar author Spalletta, Gianfranco author Spottke, Annika author Squassina, Alessio author Stordal, Eystein author Tartan, Juan Pablo author Tárraga, Lluís author Tesí, Niccolo author Thalamuthu, Anbupalam author Thomas, Tegos author Tosto, Giuseppe author Traykov, Latchezar author Tremolizzo, Lucio author Tybjærg-Hansen, Anne author Uitterlinden, Andre author Ullgren, Abbe author Ulstein, Ingun author Valero, Sergi author Valladares, Otto author Broeckhoven, Christine Van author Vance, Jeffery author Vardarajan, Badri N author van der Lugt, Aad author Dongen, Jasper Van author van Rooij, Jeroen author van Swieten, John author Vandenberghe, Rik author Verhey, Frans author Vidal, Jean-Sébastien author Vogelgsang, Jonathan author Vyhnalek, Martin author Wagner, Michael author Wallon, David author Wang, Li-San author Wang, Ruiqi author Weinhold, Leonie author Wiltfang, Jens author Windle, Gill author Woods, Bob author Yannakoulia, Mary author Zare, Habil author Zhao, Yi author Zhang, Xiaoling author Zhu, Congcong author Zulaica, Miren author Farrer, Lindsay A author Psaty, Bruce M author Ghanbari, Mohsen author Raj, Towfique author Sachdev, Perminder author Mather, Karen author Jessen, Frank author Ikram, M Arfan author de Mendonça, Alexandre author Hort, Jakub author Tsolaki, Magda author Pericak-Vance, Margaret A author Amouyel, Philippe author Williams, Julie author Frikke-Schmidt, Ruth author Clarimón, Jordi author Deleuze, Jean-François author Rossi, Giacomina author Seshadri, Sudha author Andreassen, Ole A author Ingelsson, Martin author Hiltunen, Mikko author Sleegers, Kristel author Schellenberg, Gerard D author van Duijn, Cornelia M author Sims, Rebecca author van der Flier, Wiesje M author Ruiz, Agustín author Ramirez, Alfredo author Lambert, Jean-Charles funder University Children’s Hospital Basel (Suiza) funder Lille Métropole Communauté Urbaine funder Government of France funder Institut National de la Santé et de la Recherche Médicale (Francia) funder Institut Pasteur 2022-11-14T10:20:03Z 2022-11-14T10:20:03Z 2022-04 Nat Genet. 2022 Apr;54(4):412-436. 10.1038/s41588-022-01024-z 1546-1718 Nature genetics 35379992 http://hdl.handle.net/20.500.12105/15124 Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. eng New insights into the genetic etiology of Alzheimer's disease and related dementias research article 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 URL https://repisalud.isciii.es/bitstreams/a086ec2b-1b15-401b-95af-cfd7671f58e2/download File MD5 993f468165041ae67000e72444a947fe 5163465 application/pdf NewInsightsGeneticEtiologyAlzheimer_2022.pdf URL https://repisalud.isciii.es/bitstreams/63a89694-af95-4fc2-bb9c-d0fc1a5b13c0/download File MD5 71e1f821fcd73ef190ef2306ffb2ff03 190067 text/plain NewInsightsGeneticEtiologyAlzheimer_2022.pdf.txt