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

Scientific publication - Journal Article uoadl:3219151 90 Read counter

Unit:
NKUA research material
Title:
New insights into the genetic etiology of Alzheimer's disease and related dementias
Languages of Item:
English
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 ε4 allele. © 2022. The Author(s).
Publication year:
2022
Authors:
Bellenguez, C.
Küçükali, F.
Jansen, I.E.
Kleineidam, L.
Moreno-Grau, S.
Amin, N.
Naj, A.C.
Campos-Martin, R.
Grenier-Boley, B.
Andrade, V.
Holmans, P.A.
Boland, A.
Damotte, V.
van der Lee, S.J.
Costa, M.R.
Kuulasmaa, T.
Yang, Q.
de Rojas, I.
Bis, J.C.
Yaqub, A.
Prokic, I.
Chapuis, J.
Ahmad, S.
Giedraitis, V.
Aarsland, D.
Garcia-Gonzalez, P.
Abdelnour, C.
Alarcón-Martín, E.
Alcolea, D.
Alegret, M.
Alvarez, I.
Álvarez, V.
Armstrong, N.J.
Tsolaki, A.
Antúnez, C.
Appollonio, I.
Arcaro, M.
Archetti, S.
Pastor, A.A.
Arosio, B.
Athanasiu, L.
Bailly, H.
Banaj, N.
Baquero, M.
Barral, S.
Beiser, A.
Pastor, A.B.
Below, J.E.
Benchek, P.
Benussi, L.
Berr, C.
Besse, C.
Bessi, V.
Binetti, G.
Bizarro, A.
Blesa, R.
Boada, M.
Boerwinkle, E.
Borroni, B.
Boschi, S.
Bossù, P.
Bråthen, G.
Bressler, J.
Bresner, C.
Brodaty, H.
Brookes, K.J.
Brusco, L.I.
Buiza-Rueda, D.
Bûrger, K.
Burholt, V.
Bush, W.S.
Calero, M.
Cantwell, L.B.
Chene, G.
Chung, J.
Cuccaro, M.L.
Carracedo, Á.
Cecchetti, R.
Cervera-Carles, L.
Charbonnier, C.
Chen, H.-H.
Chillotti, C.
Ciccone, S.
Claassen, J.A.H.R.
Clark, C.
Conti, E.
Corma-Gómez, A.
Costantini, E.
Custodero, C.
Daian, D.
Dalmasso, M.C.
Daniele, A.
Dardiotis, E.
Dartigues, J.-F.
de Deyn, P.P.
de Paiva Lopes, K.
de Witte, L.D.
Debette, S.
Deckert, J.
Del Ser, T.
Denning, N.
DeStefano, A.
Dichgans, M.
Diehl-Schmid, J.
Diez-Fairen, M.
Rossi, P.D.
Djurovic, S.
Duron, E.
Düzel, E.
Dufouil, C.
Eiriksdottir, G.
Engelborghs, S.
Escott-Price, V.
Espinosa, A.
Ewers, M.
Faber, K.M.
Fabrizio, T.
Nielsen, S.F.
Fardo, D.W.
Farotti, L.
Fenoglio, C.
Fernández-Fuertes, M.
Ferrari, R.
Ferreira, C.B.
Ferri, E.
Fin, B.
Fischer, P.
Fladby, T.
Fließbach, K.
Fongang, B.
Fornage, M.
Fortea, J.
Foroud, T.M.
Fostinelli, S.
Fox, N.C.
Franco-Macías, E.
Bullido, M.J.
Frank-García, A.
Froelich, L.
Fulton-Howard, B.
Galimberti, D.
García-Alberca, J.M.
García-González, P.
Garcia-Madrona, S.
Garcia-Ribas, G.
Ghidoni, R.
Giegling, I.
Giorgio, G.
Goate, A.M.
Goldhardt, O.
Gomez-Fonseca, D.
González-Pérez, A.
Graff, C.
Grande, G.
Green, E.
Grimmer, T.
Grünblatt, E.
Grunin, M.
Gudnason, V.
Guetta-Baranes, T.
Haapasalo, A.
Hadjigeorgiou, G.
Haines, J.L.
Hamilton-Nelson, K.L.
Hampel, H.
Hanon, O.
Hardy, J.
Hartmann, A.M.
Hausner, L.
Harwood, J.
Heilmann-Heimbach, S.
Helisalmi, S.
Heneka, M.T.
Hernández, I.
Herrmann, M.J.
Hoffmann, P.
Holmes, C.
Holstege, H.
Vilas, R.H.
Hulsman, M.
Humphrey, J.
Biessels, G.J.
Jian, X.
Johansson, C.
Jun, G.R.
Kastumata, Y.
Kauwe, J.
Kehoe, P.G.
Kilander, L.
Ståhlbom, A.K.
Kivipelto, M.
Koivisto, A.
Kornhuber, J.
Kosmidis, M.H.
Kukull, W.A.
Kuksa, P.P.
Kunkle, B.W.
Kuzma, A.B.
Lage, C.
Laukka, E.J.
Launer, L.
Lauria, A.
Lee, C.-Y.
Lehtisalo, J.
Lerch, O.
Lleó, A.
Longstreth, W., Jr
Lopez, O.
de Munain, A.L.
Love, S.
Löwemark, M.
Luckcuck, L.
Lunetta, K.L.
Ma, Y.
Macías, J.
MacLeod, C.A.
Maier, W.
Mangialasche, F.
Spallazzi, M.
Marquié, M.
Marshall, R.
Martin, E.R.
Montes, A.M.
Rodríguez, C.M.
Masullo, C.
Mayeux, R.
Mead, S.
Mecocci, P.
Medina, M.
Meggy, A.
Mehrabian, S.
Mendoza, S.
Menéndez-González, M.
Mir, P.
Moebus, S.
Mol, M.
Molina-Porcel, L.
Montrreal, L.
Morelli, L.
Moreno, F.
Morgan, K.
Mosley, T.
Nöthen, M.M.
Muchnik, C.
Mukherjee, S.
Nacmias, B.
Ngandu, T.
Nicolas, G.
Nordestgaard, B.G.
Olaso, R.
Orellana, A.
Orsini, M.
Ortega, G.
Padovani, A.
Paolo, C.
Papenberg, G.
Parnetti, L.
Pasquier, F.
Pastor, P.
Peloso, G.
Pérez-Cordón, A.
Pérez-Tur, J.
Pericard, P.
Peters, O.
Pijnenburg, Y.A.L.
Pineda, J.A.
Piñol-Ripoll, G.
Pisanu, C.
Polak, T.
Popp, J.
Posthuma, D.
Priller, J.
Puerta, R.
Quenez, O.
Quintela, I.
Thomassen, J.Q.
Rábano, A.
Rainero, I.
Rajabli, F.
Ramakers, I.
Real, L.M.
Reinders, M.J.T.
Reitz, C.
Reyes-Dumeyer, D.
Ridge, P.
Riedel-Heller, S.
Riederer, P.
Roberto, N.
Rodriguez-Rodriguez, E.
Rongve, A.
Allende, I.R.
Rosende-Roca, M.
Royo, J.L.
Rubino, E.
Rujescu, D.
Sáez, M.E.
Sakka, P.
Saltvedt, I.
Sanabria, Á.
Sánchez-Arjona, M.B.
Sanchez-Garcia, F.
Juan, P.S.
Sánchez-Valle, R.
Sando, S.B.
Sarnowski, C.
Satizabal, C.L.
Scamosci, M.
Scarmeas, N.
Scarpini, E.
Scheltens, P.
Scherbaum, N.
Scherer, M.
Schmid, M.
Schneider, A.
Schott, J.M.
Selbæk, G.
Seripa, D.
Serrano, M.
Sha, J.
Shadrin, A.A.
Skrobot, O.
Slifer, S.
Snijders, G.J.L.
Soininen, H.
Solfrizzi, V.
Solomon, A.
Song, Y.
Sorbi, S.
Sotolongo-Grau, O.
Spalletta, G.
Spottke, A.
Squassina, A.
Stordal, E.
Tartan, J.P.
Tárraga, L.
Tesí, N.
Thalamuthu, A.
Thomas, T.
Tosto, G.
Traykov, L.
Tremolizzo, L.
Tybjærg-Hansen, A.
Uitterlinden, A.
Ullgren, A.
Ulstein, I.
Valero, S.
Valladares, O.
Broeckhoven, C.V.
Vance, J.
Vardarajan, B.N.
van der Lugt, A.
Dongen, J.V.
van Rooij, J.
van Swieten, J.
Vandenberghe, R.
Verhey, F.
Vidal, J.-S.
Vogelgsang, J.
Vyhnalek, M.
Wagner, M.
Wallon, D.
Wang, L.-S.
Wang, R.
Weinhold, L.
Wiltfang, J.
Windle, G.
Woods, B.
Yannakoulia, M.
Zare, H.
Zhao, Y.
Zhang, X.
Zhu, C.
Zulaica, M.
Farrer, L.A.
Psaty, B.M.
Ghanbari, M.
Raj, T.
Sachdev, P.
Mather, K.
Jessen, F.
Ikram, M.A.
de Mendonça, A.
Hort, J.
Tsolaki, M.
Pericak-Vance, M.A.
Amouyel, P.
Williams, J.
Frikke-Schmidt, R.
Clarimon, J.
Deleuze, J.-F.
Rossi, G.
Seshadri, S.
Andreassen, O.A.
Ingelsson, M.
Hiltunen, M.
Sleegers, K.
Schellenberg, G.D.
van Duijn, C.M.
Sims, R.
van der Flier, W.M.
Ruiz, A.
Ramirez, A.
Lambert, J.-C.
EADB
GR@ACE
DEGESCO
EADI
GERAD
Demgene
FinnGen
ADGC
CHARGE
Journal:
Nature Genetics
Publisher:
NLM (Medline)
Volume:
54
Number:
4
Pages:
412-436
Keywords:
tau protein, Alzheimer disease; cognitive defect; genetics; genome-wide association study; human; pathology; psychology, Alzheimer Disease; Cognitive Dysfunction; Genome-Wide Association Study; Humans; tau Proteins
Official URL (Publisher):
DOI:
10.1038/s41588-022-01024-z
The digital material of the item is not available.