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New insights into the genetic etiology of Alzheimer's disease and related dementias

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Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Bellenguez, Celine
  • Kucukali, Fahri
  • Jansen, Iris E.
  • Kleineidam, Luca
  • Moreno-Grau, Sonia
  • Amin, Najaf
  • Naj, Adam C.
  • Campos-Martin, Rafael
  • Grenier-Boley, Benjamin
  • Andrade, Victor
  • Holmans, Peter A.
  • Boland, Anne
  • Damotte, Vincent
  • van der Lee, Sven J.
  • Costa, Marcos R.
  • Kuulasmaa, Teemu
  • Yang, Qiong
  • De Rojas, Itziar
  • Bis, Joshua C.
  • Yaqub, Amber
  • Prokic, Ivana
  • Chapuis, Julien
  • Ahmad, Shahzad
  • Giedraitis, Vilmantas
  • Aarsland, Dag
  • Garcia-Gonzalez, Pablo
  • Abdelnour, Carla
  • Alarcon-Martin, Emilio
  • Alcolea, Daniel
  • Alegret, Montserrat
  • Alvarez, Ignacio
  • Alvarez, Victoria
  • Armstrong, Nicola J.
  • Tsolaki, Anthoula
  • Antunez, Carmen
  • Appollonio, Ildebrando
  • Arcaro, Marina
  • Archetti, Silvana
  • Arias Pastor, Alfonso
  • Arosio, Beatrice
  • Athanasiu, Lavinia
  • Bailly, Henri
  • Banaj, Nerisa
  • Barral, Sandra
  • Beiser, Alexa
  • Pastor, Ana Belen
  • Below, Jennifer E.
  • Benchek, Penelope
  • Benussi, Luisa
  • Berr, Claudine
  • Besse, Celine
  • Bessi, Valentina
  • Binetti, Giuliano
  • Bizarro, Alessandra
  • Blesa, Rafael
  • Boada, Merce
  • Boerwinkle, Eric
  • Borroni, Barbara
  • Boschi, Silvia
  • Bossu, Paola
  • Brathen, Geir
  • Bressler, Jan
  • Bresner, Catherine
  • Brodaty, Henry
  • Brookes, Keeley J.
  • Ignacio Brusco, Luis
  • Buiza-Rueda, Dolores
  • Burger, Katharina
  • Burholt, Vanessa
  • Bush, William S.
  • Calero, Miguel
  • Cantwell, Laura B.
  • Chene, Genevieve
  • Chung, Jaeyoon
  • Cuccaro, Michael L.
  • Cecchetti, Roberta
  • Cervera-Carles, Laura
  • Charbonnier, Camille
  • Chen, Hung-Hsin
  • Chillotti, Caterina
  • Ciccone, Simona
  • Claassen, Jurgen A. H. R.
  • Clark, Christopher
  • Conti, Elisa
  • Corma-Gomez, Anais
  • Costantini, Emanuele
  • Custodero, Carlo
  • Daian, Delphine
  • Dalmasso, Maria Carolina
  • Daniele, Antonio
  • Dardiotis, Efthimios
  • Dartigues, Jean-Francois
  • de Deyn, Peter Paul
  • Lopes, Katia de Paiva
  • De Witte, Lot D.
  • Debette, Stephanie
  • Deckert, Jurgen
  • del Ser, Teodoro
  • Denning, Nicola
  • Destefano, Anita
  • Dichgans, Martin
  • Diehl-Schmid, Janine
  • Diez-Fairen, Monica
  • Rossi, Paolo Dionigi
  • Djurovic, Srdjan
  • Duron, Emmanuelle
  • Duzel, Emrah
  • Dufouil, Carole
  • Eiriksdottir, Gudny
  • Engelborghs, Sebastiaan
  • Escott-Price, Valentina
  • Espinosa, Ana
  • Ewers, Michael
  • Faber, Kelley M.
  • Fabrizio, Tagliavini
  • Nielsen, Sune Fallgaard
  • Fardo, David W.
  • Farotti, Lucia
  • Fenoglio, Chiara
  • Fernandez-Fuertes, Marta
  • Ferrari, Raffaele
  • Ferreira, Catarina B.
  • Ferri, Evelyn
  • Fin, Bertrand
  • Fischer, Peter
  • Fladby, Tormod
  • Fliessbach, Klaus
  • Fongang, Bernard
  • Fornage, Myriam
  • Fortea, Juan
  • Foroud, Tatiana M.
  • Fostinelli, Silvia
  • Fox, Nick C.
  • Franco-Macias, Emlio
  • Bullido, Maria J.
  • Frank-Garcia, Ana
  • Froelich, Lutz
  • Fulton-Howard, Brian
  • Galimberti, Daniela
  • Maria Garcia-Alberca, Jose
  • Garcia-Madrona, Sebastian
  • Garcia-Ribas, Guillermo
  • Ghidoni, Roberta
  • Giegling, Ina
  • Giorgio, Giaccone
  • Goate, Alison M.
  • Goldhardt, Oliver
  • Gomez-Fonseca, Duber
  • Gonzalez-Perez, Antonio
  • Graff, Caroline
  • Grande, Giulia
  • Green, Emma
  • Grimmer, Timo
  • Grunblatt, Edna
  • Grunin, Michelle
  • Gudnason, Vilmundur
  • Guetta-Baranes, Tamar
  • Haapasalo, Annakaisa
  • Hadjigeorgiou, Georgios
  • Haines, Jonathan L.
  • Hamilton-Nelson, Kara L.
  • Hampel, Harald
  • Hanon, Olivier
  • Hardy, John
  • Hartmann, Annette M.
  • Hausner, Lucrezia
  • Harwood, Janet
  • Heilmann-Heimbach, Stefanie
  • Helisalmi, Seppo
  • Heneka, Michael T.
  • Hernandez, Isabel
  • Herrmann, Martin J.
  • Hoffmann, Per
  • Holmes, Clive
  • Holstege, Henne
  • Huerto Vilas, Raquel
  • Hulsman, Marc
  • Humphrey, Jack
  • Biessels, Geert Jan
  • Jian, Xueqiu
  • Johansson, Charlotte
  • Jun, Gyungah R.
  • Kastumata, Yuriko
  • Kauwe, John
  • Kehoe, Patrick G.
  • Kilander, Lena
  • Stahlbom, Anne Kinhult
  • Kivipelto, Miia
  • Koivisto, Anne
  • Kornhuber, Johannes
  • Kosmidis, Mary H.
  • Kukull, Walter A.
  • Kuksa, Pavel P.
  • Kunkle, Brian W.
  • Kuzma, Amanda B.
  • Lage, Carmen
  • Laukka, Erika J.
  • Launer, Lenore
  • Lauria, Alessandra
  • Lee, Chien-Yueh
  • Lehtisalo, Jenni
  • Lerch, Ondrej
  • Lleo, Alberto
  • Longstreth, Jr., William
  • Lopez, Oscar
  • Lopez de Munain, Adolfo
  • Love, Seth
  • Lowemark, Malin
  • Luckcuck, Lauren
  • Lunetta, Kathryn L.
  • Ma, Yiyi
  • Macias, Juan
  • Macleod, Catherine A.
  • Maier, Wolfgang
  • Mangialasche, Francesca
  • Spallazzi, Marco
  • Marquie, Marta
  • Marshall, Rachel
  • Martin, Eden R.
  • Martin Montes, Angel
  • Martinez Rodriguez, Carmen
  • Masullo, Carlo
  • Mayeux, Richard
  • Mead, Simon
  • Mecocci, Patrizia
  • Medina, Miguel
  • Meggy, Alun
  • Mehrabian, Shima
  • Mendoza, Silvia
  • Menendez-Gonzalez, Manuel
  • Mir, Pablo
  • Moebus, Susanne
  • Mol, Merel
  • Molina-Porcel, Laura
  • Montrreal, Laura
  • Morelli, Laura
  • Moreno, Fermin
  • Morgan, Kevin
  • Mosley, Thomas
  • Nothen, Markus M.
  • Muchnik, Carolina
  • Mukherjee, Shubhabrata
  • Nacmias, Benedetta
  • Ngandu, Tiia
  • Nicolas, Gael
  • Nordestgaard, Borge G.
  • Olaso, Robert
  • Orellana, Adelina
  • Orsini, Michela
  • Ortega, Gemma
  • Padovani, Alessandro
  • Paolo, Caffarra
  • Papenberg, Goran
  • Parnetti, Lucilla
  • Pasquier, Florence
  • Pastor, Pau
  • Peloso, Gina
  • Perez-Cordon, Alba
  • Pericard, Pierre
  • Peters, Oliver
  • Pijnenburg, Yolande A. L.
  • Pineda, Juan A.
  • Pinol-Ripoll, Gerard
  • Pisanu, Laudia
  • Polak, Thomas
  • Popp, Julius
  • Posthuma, Danielle
  • Priller, Josef
  • Puerta, Raquel
  • Quenez, Olivier
  • Quintela, Ines
  • Thomassen, Jesper Qvist
  • Rabano, Alberto
  • Rainero, Innocenzo
  • Rajabli, Farid
  • Ramakers, Inez
  • Real, Luis M.
  • Reinders, Marcel J. T.
  • Reitz, Christiane
  • Reyes-Dumeyer, Dolly
  • Ridge, Perry
  • Riedel-Heller, Steffi
  • Riederer, Peter
  • Roberto, Natalia
  • Rodriguez-Rodriguez, Eloy
  • Rongve, Arvid
  • Rosas Allende, Irene
  • Rosende-Roca, Maitee
  • Luis Royo, Jose
  • Rubino, Elisa
  • Rujescu, Dan
  • Eugenia Saez, Maria
  • Sakka, Paraskevi
  • Saltvedt, Ingvild
  • Bernal Sanchez-Arjona, Maria
  • Sanchez-Garcia, Florentino
  • Sanchez Juan, Pascual
  • Sanchez-Valle, Raquel
  • Sando, Sigrid B.
  • Sarnowski, Chloe
  • Satizabal, Claudia L.
  • Scamosci, Michela
  • Scarmeas, Nikolaos
  • Scarpini, Elio
  • Scheltens, Philip
  • Scherbaum, Norbert
  • Scherer, Martin
  • Schmid, Matthias
  • Schneider, Anja
  • Schott, Jonathan M.
  • Selbaek, Geir
  • Seripa, Davide
  • Serrano, Manuel
  • Sha, Jin
  • Shadrin, Alexey A.
  • Skrobot, Olivia
  • Slifer, Susan
  • Snijders, Gijsje J. L.
  • Soininen, Hilkka
  • Solfrizzi, Vincenzo
  • Solomon, Alina
  • Song, Yeunjoo
  • Sorbi, Sandro
  • Sotolongo-Grau, Oscar
  • Spalletta, Gianfranco
  • Spottke, Annika
  • Squassina, Alessio
  • Stordal, Eystein
  • Pablo Tartan, Juan
  • Tarraga, Lluis
  • Tesi, Niccolo
  • Thalamuthu, Anbupalam
  • Thomas, Tegos
  • Tosto, Giuseppe
  • Traykov, Latchezar
  • Tremolizzo, Lucio
  • Tybjaerg-Hansen, Anne
  • Uitterlinden, Andre
  • Ullgren, Abbe
  • Ulstein, Ingun
  • Valero, Sergi
  • Valladares, Otto
  • Van Broeckhoven, Christine
  • Vance, Jeffery
  • Vardarajan, Badri N.
  • van der Lugt, Aad
  • Van Dongen, Jasper
  • van Rooij, Jeroen
  • van Swieten, John
  • Vandenberghe, Rik
  • Verhey, Frans
  • Vidal, Jean-Sebastien
  • Vogelgsang, Jonathan
  • Vyhnalek, Martin
  • Wagner, Michael
  • Wallon, David
  • Wang, Li-San
  • Wang, Ruiqi
  • Weinhold, Leonie
  • Wiltfang, Jens
  • Windle, Gill
  • Woods, Bob
  • Yannakoulia, Mary
  • Zare, Habil
  • Zhao, Yi
  • Zhang, Xiaoling
  • Zhu, Congcong
  • Zulaica, Miren
  • Farrer, Lindsay A.
  • Psaty, Bruce M.
  • Ghanbari, Mohsen
  • Raj, Towfique
  • Sachdev, Perminder
  • Mather, Karen
  • Jessen, Frank
  • Ikram, M. Arfan
  • de Mendonca, Alexandre
  • Hort, Jakub
  • Tsolaki, Magda
  • Pericak-Vance, Margaret A.
  • Amouyel, Philippe
  • Williams, Julie
  • Frikke-Schmidt, Ruth
  • Clarimon, Jordi
  • Deleuze, Jean-Francois
  • Rossi, Giacomina
  • Seshadri, Sudha
  • Andreassen, Ole A.
  • Ingelsson, Martin
  • Hiltunen, Mikko
  • Sleegers, Kristel
  • Schellenberg, Gerard D.
  • van Duijn, Cornelia M.
  • Sims, Rebecca
  • van der Flier, Wiesje M.
  • Ruiz, Agustin
  • Ramirez, Alfredo
  • Lambert, Jean-Charles
  • EADB
  • DEGESCO
  • EADI
  • GERAD
  • Demgene
  • FinnGen
  • ADGC
  • CHARGE
  • GR ACE

Grupos

Abstract

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 epsilon 4 allele. Meta-analysis of genome-wide association studies on Alzheimer's disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer's disease and dementia.

© 2022. The Author(s).

Datos de la publicación

ISSN/ISSNe:
1061-4036, 1546-1718

NATURE GENETICS  NATURE PORTFOLIO

Tipo:
Article
Páginas:
412-412
PubMed:
35379992
Factor de Impacto:
16,517 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 1.692

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Keywords

  • GENOME-WIDE ASSOCIATION; NECROSIS-FACTOR-ALPHA; RISK LOCI; PREDICTION MODELS; AMYLOID-BETA; METAANALYSIS; VARIANTS; GENERATION; IMPUTATION; RESPONSES

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