@article{3219151,
    title = "New insights into the genetic etiology of Alzheimer's disease and related dementias",
    author = "Bellenguez, C. and Küçükali, F. and Jansen, I.E. and Kleineidam, L. and Moreno-Grau, S. and Amin, N. and Naj, A.C. and Campos-Martin, R. and Grenier-Boley, B. and Andrade, V. and Holmans, P.A. and Boland, A. and Damotte, V. and van der Lee, S.J. and Costa, M.R. and Kuulasmaa, T. and Yang, Q. and de Rojas, I. and Bis, J.C. and Yaqub, A. and Prokic, I. and Chapuis, J. and Ahmad, S. and Giedraitis, V. and Aarsland, D. and Garcia-Gonzalez, P. and Abdelnour, C. and Alarcón-Martín, E. and Alcolea, D. and Alegret, M. and Alvarez, I. and Álvarez, V. and Armstrong, N.J. and Tsolaki, A. and Antúnez, C. and Appollonio, I. and Arcaro, M. and Archetti, S. and Pastor, A.A. and Arosio, B. and Athanasiu, L. and Bailly, H. and Banaj, N. and Baquero, M. and Barral, S. and Beiser, A. and Pastor, A.B. and Below, J.E. and Benchek, P. and Benussi, L. and Berr, C. and Besse, C. and Bessi, V. and Binetti, G. and Bizarro, A. and Blesa, R. and Boada, M. and Boerwinkle, E. and Borroni, B. and Boschi, S. and Bossù, P. and Bråthen, G. and Bressler, J. and Bresner, C. and Brodaty, H. and Brookes, K.J. and Brusco, L.I. and Buiza-Rueda, D. and Bûrger, K. and Burholt, V. and Bush, W.S. and Calero, M. and Cantwell, L.B. and Chene, G. and Chung, J. and Cuccaro, M.L. and Carracedo, Á. and Cecchetti, R. and Cervera-Carles, L. and Charbonnier, C. and Chen, H.-H. and Chillotti, C. and Ciccone, S. and Claassen, J.A.H.R. and Clark, C. and Conti, E. and Corma-Gómez, A. and Costantini, E. and Custodero, C. and Daian, D. and Dalmasso, M.C. and Daniele, A. and Dardiotis, E. and Dartigues, J.-F. and de Deyn, P.P. and de Paiva Lopes, K. and de Witte, L.D. and Debette, S. and Deckert, J. and Del Ser, T. and Denning, N. and DeStefano, A. and Dichgans, M. and Diehl-Schmid, J. and Diez-Fairen, M. and Rossi, P.D. and Djurovic, S. and Duron, E. and Düzel, E. and Dufouil, C. and Eiriksdottir, G. and Engelborghs, S. and Escott-Price, V. and Espinosa, A. and Ewers, M. and Faber, K.M. and Fabrizio, T. and Nielsen, S.F. and Fardo, D.W. and Farotti, L. and Fenoglio, C. and Fernández-Fuertes, M. and Ferrari, R. and Ferreira, C.B. and Ferri, E. and Fin, B. and Fischer, P. and Fladby, T. and Fließbach, K. and Fongang, B. and Fornage, M. and Fortea, J. and Foroud, T.M. and Fostinelli, S. and Fox, N.C. and Franco-Macías, E. and Bullido, M.J. and Frank-García, A. and Froelich, L. and Fulton-Howard, B. and Galimberti, D. and García-Alberca, J.M. and García-González, P. and Garcia-Madrona, S. and Garcia-Ribas, G. and Ghidoni, R. and Giegling, I. and Giorgio, G. and Goate, A.M. and Goldhardt, O. and Gomez-Fonseca, D. and González-Pérez, A. and Graff, C. and Grande, G. and Green, E. and Grimmer, T. and Grünblatt, E. and Grunin, M. and Gudnason, V. and Guetta-Baranes, T. and Haapasalo, A. and Hadjigeorgiou, G. and Haines, J.L. and Hamilton-Nelson, K.L. and Hampel, H. and Hanon, O. and Hardy, J. and Hartmann, A.M. and Hausner, L. and Harwood, J. and Heilmann-Heimbach, S. and Helisalmi, S. and Heneka, M.T. and Hernández, I. and Herrmann, M.J. and Hoffmann, P. and Holmes, C. and Holstege, H. and Vilas, R.H. and Hulsman, M. and Humphrey, J. and Biessels, G.J. and Jian, X. and Johansson, C. and Jun, G.R. and Kastumata, Y. and Kauwe, J. and Kehoe, P.G. and Kilander, L. and Ståhlbom, A.K. and Kivipelto, M. and Koivisto, A. and Kornhuber, J. and Kosmidis, M.H. and Kukull, W.A. and Kuksa, P.P. and Kunkle, B.W. and Kuzma, A.B. and Lage, C. and Laukka, E.J. and Launer, L. and Lauria, A. and Lee, C.-Y. and Lehtisalo, J. and Lerch, O. and Lleó, A. and Longstreth, W., Jr and Lopez, O. and de Munain, A.L. and Love, S. and Löwemark, M. and Luckcuck, L. and Lunetta, K.L. and Ma, Y. and Macías, J. and MacLeod, C.A. and Maier, W. and Mangialasche, F. and Spallazzi, M. and Marquié, M. and Marshall, R. and Martin, E.R. and Montes, A.M. and Rodríguez, C.M. and Masullo, C. and Mayeux, R. and Mead, S. and Mecocci, P. and Medina, M. and Meggy, A. and Mehrabian, S. and Mendoza, S. and Menéndez-González, M. and Mir, P. and Moebus, S. and Mol, M. and Molina-Porcel, L. and Montrreal, L. and Morelli, L. and Moreno, F. and Morgan, K. and Mosley, T. and Nöthen, M.M. and Muchnik, C. and Mukherjee, S. and Nacmias, B. and Ngandu, T. and Nicolas, G. and Nordestgaard, B.G. and Olaso, R. and Orellana, A. and Orsini, M. and Ortega, G. and Padovani, A. and Paolo, C. and Papenberg, G. and Parnetti, L. and Pasquier, F. and Pastor, P. and Peloso, G. and Pérez-Cordón, A. and Pérez-Tur, J. and Pericard, P. and Peters, O. and Pijnenburg, Y.A.L. and Pineda, J.A. and Piñol-Ripoll, G. and Pisanu, C. and Polak, T. and Popp, J. and Posthuma, D. and Priller, J. and Puerta, R. and Quenez, O. and Quintela, I. and Thomassen, J.Q. and Rábano, A. and Rainero, I. and Rajabli, F. and Ramakers, I. and Real, L.M. and Reinders, M.J.T. and Reitz, C. and Reyes-Dumeyer, D. and Ridge, P. and Riedel-Heller, S. and Riederer, P. and Roberto, N. and Rodriguez-Rodriguez, E. and Rongve, A. and Allende, I.R. and Rosende-Roca, M. and Royo, J.L. and Rubino, E. and Rujescu, D. and Sáez, M.E. and Sakka, P. and Saltvedt, I. and Sanabria, Á. and Sánchez-Arjona, M.B. and Sanchez-Garcia, F. and Juan, P.S. and Sánchez-Valle, R. and Sando, S.B. and Sarnowski, C. and Satizabal, C.L. and Scamosci, M. and Scarmeas, N. and Scarpini, E. and Scheltens, P. and Scherbaum, N. and Scherer, M. and Schmid, M. and Schneider, A. and Schott, J.M. and Selbæk, G. and Seripa, D. and Serrano, M. and Sha, J. and Shadrin, A.A. and Skrobot, O. and Slifer, S. and Snijders, G.J.L. and Soininen, H. and Solfrizzi, V. and Solomon, A. and Song, Y. and Sorbi, S. and Sotolongo-Grau, O. and Spalletta, G. and Spottke, A. and Squassina, A. and Stordal, E. and Tartan, J.P. and Tárraga, L. and Tesí, N. and Thalamuthu, A. and Thomas, T. and Tosto, G. and Traykov, L. and Tremolizzo, L. and Tybjærg-Hansen, A. and Uitterlinden, A. and Ullgren, A. and Ulstein, I. and Valero, S. and Valladares, O. and Broeckhoven, C.V. and Vance, J. and Vardarajan, B.N. and van der Lugt, A. and Dongen, J.V. and van Rooij, J. and van Swieten, J. and Vandenberghe, R. and Verhey, F. and Vidal, J.-S. and Vogelgsang, J. and Vyhnalek, M. and Wagner, M. and Wallon, D. and Wang, L.-S. and Wang, R. and Weinhold, L. and Wiltfang, J. and Windle, G. and Woods, B. and Yannakoulia, M. and Zare, H. and Zhao, Y. and Zhang, X. and Zhu, C. and Zulaica, M. and Farrer, L.A. and Psaty, B.M. and Ghanbari, M. and Raj, T. and Sachdev, P. and Mather, K. and Jessen, F. and Ikram, M.A. and de Mendonça, A. and Hort, J. and Tsolaki, M. and Pericak-Vance, M.A. and Amouyel, P. and Williams, J. and Frikke-Schmidt, R. and Clarimon, J. and Deleuze, J.-F. and Rossi, G. and Seshadri, S. and Andreassen, O.A. and Ingelsson, M. and Hiltunen, M. and Sleegers, K. and Schellenberg, G.D. and van Duijn, C.M. and Sims, R. and van der Flier, W.M. and Ruiz, A. and Ramirez, A. and Lambert, J.-C. and EADB and GR@ACE and DEGESCO and EADI and GERAD and Demgene and FinnGen and ADGC and CHARGE",
    journal = "Nature Genetics",
    year = "2022",
    volume = "54",
    number = "4",
    pages = "412-436",
    publisher = "NLM (Medline)",
    issn = "1061-4036, 1546-1718",
    doi = "10.1038/s41588-022-01024-z",
    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",
    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)."
}