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New insights into the genetic etiology of Alzheimer's disease and related dementias
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- Bellenguez, C (author)
- Univ Lille, Facteurs Risque & Terminants Mol Malad Liees Viei, Inst Pasteur Lille, INSERM,U1167 RID AGE,CHU Lille, Lille, France
- Kucukali, F (author)
- Jansen, IE (author)
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- Kleineidam, L (author)
- Moreno-Grau, S (author)
- Amin, N (author)
- Naj, AC (author)
- Campos-Martin, R (author)
- Grenier-Boley, B (author)
- Andrade, V (author)
- Holmans, PA (author)
- Boland, A (author)
- Damotte, V (author)
- van der Lee, SJ (author)
- Costa, MR (author)
- Kuulasmaa, T (author)
- Yang, Q (author)
- De Rojas, I (author)
- Yaqub, A (author)
- Prokic, I (author)
- Chapuis, J (author)
- Abdelnour, C (author)
- Alarcon-Martin, E (author)
- Alcolea, D (author)
- Alegret, M (author)
- Alvarez, I (author)
- Alvarez, V (author)
- Armstrong, NJ (author)
- Tsolaki, A (author)
- Antunez, C (author)
- Appollonio, I (author)
- Arcaro, M (author)
- Archetti, S (author)
- Pastor, AA (author)
- Arosio, B (author)
- Athanasiu, L (author)
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- Besse, C (author)
- Bessi, V (author)
- Binetti, G (author)
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- Boada, M (author)
- Boerwinkle, E (author)
- Borroni, B (author)
- Boschi, S (author)
- Bossu, P (author)
- Brathen, G (author)
- Bressler, J (author)
- Bresner, C (author)
- Brodaty, H (author)
- Brookes, KJ (author)
- Brusco, LI (author)
- Buiza-Rueda, D (author)
- Burger, K (author)
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- Bush, WS (author)
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- Cuccaro, ML (author)
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- Chen, HH (author)
- Chillotti, C (author)
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- Claassen, JAHR (author)
- Clark, C (author)
- Conti, E (author)
- Corma-Gomez, A (author)
- Costantini, E (author)
- Custodero, C (author)
- Daian, D (author)
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- del Ser, T (author)
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- Diehl-Schmid, J (author)
- Rossi, PD (author)
- Djurovic, S (author)
- Duron, E (author)
- Duzel, E (author)
- Dufouil, C (author)
- Eiriksdottir, G (author)
- Engelborghs, S (author)
- Escott-Price, V (author)
- Espinosa, A (author)
- Ewers, M (author)
- Fabrizio, T (author)
- Nielsen, SF (author)
- Fardo, DW (author)
- Farotti, L (author)
- Fenoglio, C (author)
- Fernandez-Fuertes, M (author)
- Ferrari, R (author)
- Ferreira, CB (author)
- Ferri, E (author)
- Fin, B (author)
- Fischer, P (author)
- Fladby, T (author)
- Fliessbach, K (author)
- Fongang, B (author)
- Fornage, M (author)
- Fortea, J (author)
- Foroud, TM (author)
- Fostinelli, S (author)
- Fox, NC (author)
- Franco-Macias, E (author)
- Bullido, MJ (author)
- Frank-Garcia, A (author)
- Froelich, L (author)
- Fulton-Howard, B (author)
- Galimberti, D (author)
- Garcia-Alberca, JM (author)
- Garcia-Madrona, S (author)
- Ghidoni, R (author)
- Giegling, I (author)
- Giorgio, G (author)
- Goate, AM (author)
- Goldhardt, O (author)
- Gomez-Fonseca, D (author)
- Gonzalez-Perez, A (author)
- Green, E (author)
- Grimmer, T (author)
- Grunblatt, E (author)
- Grunin, M (author)
- Gudnason, V (author)
- Guetta-Baranes, T (author)
- Haapasalo, A (author)
- Hadjigeorgiou, G (author)
- Haines, JL (author)
- Hamilton-Nelson, KL (author)
- Hampel, H (author)
- Hanon, O (author)
- Hardy, J (author)
- Hartmann, AM (author)
- Hausner, L (author)
- Harwood, J (author)
- Heilmann-Heimbach, S (author)
- Helisalmi, S (author)
- Heneka, MT (author)
- Hernandez, I (author)
- Herrmann, MJ (author)
- Hoffmann, P (author)
- Holmes, C (author)
- Holstege, H (author)
- Vilas, RH (author)
- Hulsman, M (author)
- Humphrey, J (author)
- Biessels, GJ (author)
- Jian, XQ (author)
- Jun, GR (author)
- Kastumata, Y (author)
- Kauwe, J (author)
- Kilander, L (author)
- Stahlbom, AK (author)
- Koivisto, A (author)
- Kornhuber, J (author)
- Kosmidis, MH (author)
- Kukull, WA (author)
- Kuksa, PP (author)
- Kunkle, BW (author)
- Kuzma, AB (author)
- Lage, C (author)
- Launer, L (author)
- Lauria, A (author)
- Lee, CY (author)
- Lehtisalo, J (author)
- Lerch, O (author)
- Lleo, A (author)
- Longstreth, W (author)
- Lopez, O (author)
- de Munain, AL (author)
- Love, S (author)
- Lowemark, M (author)
- Luckcuck, L (author)
- Lunetta, KL (author)
- Ma, YY (author)
- Macias, J (author)
- Macleod, CA (author)
- Maier, W (author)
- Spallazzi, M (author)
- Marquie, M (author)
- Marshall, R (author)
- Martin, ER (author)
- Montes, AM (author)
- Rodriguez, CM (author)
- Masullo, C (author)
- Mayeux, R (author)
- Mead, S (author)
- Medina, M (author)
- Meggy, A (author)
- Mehrabian, S (author)
- Mendoza, S (author)
- Menendez-Gonzalez, M (author)
- Mir, P (author)
- Moebus, S (author)
- Mol, M (author)
- Molina-Porcel, L (author)
- Montrreal, L (author)
- Morelli, L (author)
- Moreno, F (author)
- Morgan, K (author)
- Mosley, T (author)
- Nothen, MM (author)
- Muchnik, C (author)
- Mukherjee, S (author)
- Nacmias, B (author)
- Nicolas, G (author)
- Nordestgaard, BG (author)
- Olaso, R (author)
- Orellana, A (author)
- Orsini, M (author)
- Ortega, G (author)
- Padovani, A (author)
- Paolo, C (author)
- Parnetti, L (author)
- Pasquier, F (author)
- Pastor, P (author)
- Peloso, G (author)
- Perez-Cordon, A (author)
- Perez-Tur, J (author)
- Pericard, P (author)
- Peters, O (author)
- Pijnenburg, YAL (author)
- Pineda, JA (author)
- Pinol-Ripoll, G (author)
- Pisanu, L (author)
- Polak, T (author)
- Popp, J (author)
- Posthuma, D (author)
- Priller, J (author)
- Puerta, R (author)
- Quenez, O (author)
- Quintela, I (author)
- Thomassen, JQ (author)
- Rabano, A (author)
- Rainero, I (author)
- Rajabli, F (author)
- Ramakers, I (author)
- Real, LM (author)
- Reinders, MJT (author)
- Reitz, C (author)
- Reyes-Dumeyer, D (author)
- Ridge, P (author)
- Riedel-Heller, S (author)
- Riederer, P (author)
- Roberto, N (author)
- Rodriguez-Rodriguez, E (author)
- Rongve, A (author)
- Allende, IR (author)
- Rosende-Roca, M (author)
- Royo, JL (author)
- Rubino, E (author)
- Rujescu, D (author)
- Saez, ME (author)
- Sakka, P (author)
- Saltvedt, I (author)
- Sanchez-Arjona, MB (author)
- Sanchez-Garcia, F (author)
- Juan, PS (author)
- Sanchez-Valle, R (author)
- Sando, SB (author)
- Sarnowski, C (author)
- Satizabal, CL (author)
- Scamosci, M (author)
- Scarmeas, N (author)
- Scarpini, E (author)
- Scheltens, P (author)
- Scherbaum, N (author)
- Scherer, M (author)
- Schmid, M (author)
- Schneider, A (author)
- Schott, JM (author)
- Selbaek, G (author)
- Seripa, D (author)
- Serrano, M (author)
- Sha, J (author)
- Shadrin, AA (author)
- Skrobot, O (author)
- Slifer, S (author)
- Snijders, GJL (author)
- Soininen, H (author)
- Solfrizzi, V (author)
- Song, Y (author)
- Sorbi, S (author)
- Sotolongo-Grau, O (author)
- Spalletta, G (author)
- Spottke, A (author)
- Squassina, A (author)
- Stordal, E (author)
- Tartan, JP (author)
- Tarraga, L (author)
- Tesi, N (author)
- Thalamuthu, A (author)
- Thomas, T (author)
- Tosto, G (author)
- Traykov, L (author)
- Tremolizzo, L (author)
- Tybjaeg-Hansen, A (author)
- Uitterlinden, A (author)
- Ulstein, I (author)
- Valero, S (author)
- Valladares, O (author)
- Van Broeckhoven, C (author)
- Vance, J (author)
- Vardarajan, BN (author)
- van der Lugt, A (author)
- Van Dongen, J (author)
- van Rooij, J (author)
- van Swieten, J (author)
- Vandenberghe, R (author)
- Verhey, F (author)
- Vidal, JS (author)
- Vogelgsang, J (author)
- Vyhnalek, M (author)
- Wagner, M (author)
- Wallon, D (author)
- Wang, LS (author)
- Wang, RQ (author)
- Weinhold, L (author)
- Wiltfang, J (author)
- Windle, G (author)
- Woods, B (author)
- Yannakoulia, M (author)
- Zare, H (author)
- Zhao, Y (author)
- Zhang, XL (author)
- Zhu, CC (author)
- Zulaica, M (author)
- Farrer, LA (author)
- Psaty, BM (author)
- Ghanbari, M (author)
- Raj, T (author)
- Sachdev, P (author)
- Mather, K (author)
- Jessen, F (author)
- Ikram, MA (author)
- de Mendonca, A (author)
- Hort, J (author)
- Tsolaki, M (author)
- Pericak-Vance, MA (author)
- Amouyel, P (author)
- Williams, J (author)
- Frikke-Schmidt, R (author)
- Clarimon, J (author)
- Deleuze, JF (author)
- Rossi, G (author)
- Seshadri, S (author)
- Andreassen, OA (author)
- Hiltunen, M (author)
- Sleegers, K (author)
- Schellenberg, GD (author)
- van Duijn, CM (author)
- Sims, R (author)
- van der Flier, WM (author)
- Ruiz, A (author)
- Ramirez, A (author)
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- (creator_code:org_t)
- 2022-04-04
- 2022
- English.
- In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- Bellenguez, C
- Kucukali, F
- Jansen, IE
- Kleineidam, L
- Moreno-Grau, S
- Amin, N
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- Naj, AC
- Campos-Martin, R
- Grenier-Boley, B
- Andrade, V
- Holmans, PA
- Boland, A
- Damotte, V
- van der Lee, SJ
- Costa, MR
- Kuulasmaa, T
- Yang, Q
- De Rojas, I
- Bis, JC
- Yaqub, A
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- Garcia-Gonzalez, ...
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- Alarcon-Martin, ...
- Alcolea, D
- Alegret, M
- Alvarez, I
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- Armstrong, NJ
- Tsolaki, A
- Antunez, C
- Appollonio, I
- Arcaro, M
- Archetti, S
- Pastor, AA
- Arosio, B
- Athanasiu, L
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- Banaj, N
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- Pastor, AB
- Below, JE
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- Boada, M
- Boerwinkle, E
- Borroni, B
- Boschi, S
- Bossu, P
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- Bressler, J
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- Ramirez, A
- Lambert, JC
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