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

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Bellenguez, CUniv Lille, Facteurs Risque & Terminants Mol Malad Liees Viei, Inst Pasteur Lille, INSERM,U1167 RID AGE,CHU Lille, Lille, France (author)

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

Article/chapterEnglish2022

Publisher, publication year, extent ...

2022-04-04
Springer Science and Business Media LLC,2022

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LIBRIS-ID:oai:prod.swepub.kib.ki.se:149225642
http://kipublications.ki.se/Default.aspx?queryparsed=id:149225642URI
https://doi.org/10.1038/s41588-022-01024-zDOI
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-204358URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-473589URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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For complete list of authors see http://dx.doi.org/10.1038/s41588-022-01024-z
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.

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Kucukali, F (author)
Jansen, IE (author)
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)
Bis, JCKarolinska Institutet (author)
Yaqub, A (author)
Prokic, I (author)
Chapuis, J (author)
Ahmad, SKarolinska Institutet (author)
Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517 (author)
Aarsland, DKarolinska Institutet (author)
Garcia-Gonzalez, PKarolinska Institutet (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)
Bailly, H (author)
Banaj, N (author)
Baquero, M (author)
Barral, S (author)
Beiser, A (author)
Pastor, AB (author)
Below, JE (author)
Benchek, P (author)
Benussi, L (author)
Berr, C (author)
Besse, C (author)
Bessi, V (author)
Binetti, G (author)
Bizarro, A (author)
Blesa, R (author)
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)
Burholt, V (author)
Bush, WS (author)
Calero, M (author)
Cantwell, LB (author)
Chene, GKarolinska Institutet (author)
Chung, J (author)
Cuccaro, ML (author)
Cecchetti, R (author)
Cervera-Carles, L (author)
Charbonnier, C (author)
Chen, HH (author)
Chillotti, C (author)
Ciccone, S (author)
Claassen, JAHR (author)
Clark, C (author)
Conti, E (author)
Corma-Gomez, A (author)
Costantini, E (author)
Custodero, C (author)
Daian, D (author)
Dalmasso, MC (author)
Daniele, A (author)
Dardiotis, E (author)
Dartigues, JF (author)
de Deyn, PP (author)
Lopes, KD (author)
De Witte, LD (author)
Debette, S (author)
Deckert, J (author)
del Ser, T (author)
Denning, N (author)
Destefano, A (author)
Dichgans, M (author)
Diehl-Schmid, J (author)
Diez-Fairen, MKarolinska Institutet (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)
Faber, KMKarolinska Institutet (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)
Garcia-Ribas, GKarolinska Institutet,Stockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI) (author)
Ghidoni, R (author)
Giegling, I (author)
Giorgio, G (author)
Goate, AM (author)
Goldhardt, O (author)
Gomez-Fonseca, D (author)
Gonzalez-Perez, A (author)
Graff, CKarolinska Institutet (author)
Grande, GKarolinska Institutet (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)
Johansson, CKarolinska Institutet (author)
Jun, GR (author)
Kastumata, Y (author)
Kauwe, J (author)
Kehoe, PGStockholms universitet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI) (author)
Kilander, L (author)
Stahlbom, AK (author)
Kivipelto, MKarolinska Institutet (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)
Laukka, EJStockholms universitet,Karolinska Institutet,Centrum för forskning om äldre och åldrande (ARC), (tills m KI),Stockholm Gerontology Research Center, Sweden (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)
Mangialasche, FKarolinska Institutet (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)
Mecocci, PKarolinska Institutet (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)
Ngandu, TKarolinska Institutet (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)
Papenberg, GKarolinska Institutet (author)
Parnetti, L (author)
Pasquier, F (author)
Pastor, P (author)
Peloso, G (author)
Perez-Cordon, A (author)
Perez-Tur, J (author)
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Pijnenburg, YAL (author)
Pineda, JA (author)
Pinol-Ripoll, G (author)
Pisanu, L (author)
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Popp, J (author)
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Thomassen, JQ (author)
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Rajabli, F (author)
Ramakers, I (author)
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Reitz, C (author)
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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)
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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)
Solomon, AKarolinska Institutet (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)
Ullgren, AKarolinska Institutet (author)
Ulstein, I (author)
Valero, S (author)
Valladares, O (author)
Van Broeckhoven, C (author)
Vance, J (author)
Vardarajan, BN (author)
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Van Dongen, J (author)
van Rooij, J (author)
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Verhey, F (author)
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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)
Ingelsson, MartinUppsala universitet,Geriatrik(Swepub:uu)maing121 (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)
Lambert, JCUniv Lille, Facteurs Risque & Terminants Mol Malad Liees Viei, Inst Pasteur Lille, INSERM,U1167 RID AGE,CHU Lille, Lille, France (author)
Karolinska InstitutetUniv Lille, Facteurs Risque & Terminants Mol Malad Liees Viei, Inst Pasteur Lille, INSERM,U1167 RID AGE,CHU Lille, Lille, France (creator_code:org_t)

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By the author/editor: Bellenguez, C; Kucukali, F; Jansen, IE; Kleineidam, L; Moreno-Grau, S; Amin, N; show more...; 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; Prokic, I; Chapuis, J; Ahmad, S; Giedraitis, Vilm ...; Aarsland, D; Garcia-Gonzalez, ...; Abdelnour, C; Alarcon-Martin, ...; Alcolea, D; Alegret, M; Alvarez, I; Alvarez, V; Armstrong, NJ; Tsolaki, A; Antunez, C; Appollonio, I; Arcaro, M; Archetti, S; Pastor, AA; Arosio, B; Athanasiu, L; Bailly, H; Banaj, N; Baquero, M; Barral, S; Beiser, A; Pastor, AB; Below, JE; Benchek, P; Benussi, L; Berr, C; Besse, C; Bessi, V; Binetti, G; Bizarro, A; Blesa, R; Boada, M; Boerwinkle, E; Borroni, B; Boschi, S; Bossu, P; Brathen, G; Bressler, J; Bresner, C; Brodaty, H; Brookes, KJ; Brusco, LI; Buiza-Rueda, D; Burger, K; Burholt, V; Bush, WS; Calero, M; Cantwell, LB; Chene, G; Chung, J; Cuccaro, ML; Cecchetti, R; Cervera-Carles, ...; Charbonnier, C; Chen, HH; Chillotti, C; Ciccone, S; Claassen, JAHR; Clark, C; Conti, E; Corma-Gomez, A; Costantini, E; Custodero, C; Daian, D; Dalmasso, MC; Daniele, A; Dardiotis, E; Dartigues, JF; de Deyn, PP; Lopes, KD; De Witte, LD; Debette, S; Deckert, J; del Ser, T; Denning, N; Destefano, A; Dichgans, M; Diehl-Schmid, J; Diez-Fairen, M; Rossi, PD; Djurovic, S; Duron, E; Duzel, E; Dufouil, C; Eiriksdottir, G; Engelborghs, S; Escott-Price, V; Espinosa, A; Ewers, M; Faber, KM; Fabrizio, T; Nielsen, SF; Fardo, DW; Farotti, L; Fenoglio, C; Fernandez-Fuerte ...; Ferrari, R; Ferreira, CB; Ferri, E; Fin, B; Fischer, P; Fladby, T; Fliessbach, K; Fongang, B; Fornage, M; Fortea, J; Foroud, TM; Fostinelli, S; Fox, NC; Franco-Macias, E; Bullido, MJ; Frank-Garcia, A; Froelich, L; Fulton-Howard, B; Galimberti, D; Garcia-Alberca, ...; Garcia-Madrona, ...; Garcia-Ribas, G; Ghidoni, R; Giegling, I; Giorgio, G; Goate, AM; Goldhardt, O; Gomez-Fonseca, D; Gonzalez-Perez, ...; Graff, C; Grande, G; Green, E; Grimmer, T; Grunblatt, E; Grunin, M; Gudnason, V; Guetta-Baranes, ...; Haapasalo, A; Hadjigeorgiou, G; Haines, JL; Hamilton-Nelson, ...; Hampel, H; Hanon, O; Hardy, J; Hartmann, AM; Hausner, L; Harwood, J; Heilmann-Heimbac ...; Helisalmi, S; Heneka, MT; Hernandez, I; Herrmann, MJ; Hoffmann, P; Holmes, C; Holstege, H; Vilas, RH; Hulsman, M; Humphrey, J; Biessels, GJ; Jian, XQ; Johansson, C; Jun, GR; Kastumata, Y; Kauwe, J; Kehoe, PG; Kilander, L; Stahlbom, AK; Kivipelto, M; Koivisto, A; Kornhuber, J; Kosmidis, MH; Kukull, WA; Kuksa, PP; Kunkle, BW; Kuzma, AB; Lage, C; Laukka, EJ; Launer, L; Lauria, A; Lee, CY; Lehtisalo, J; Lerch, O; Lleo, A; Longstreth, W; Lopez, O; de Munain, AL; Love, S; Lowemark, M; Luckcuck, L; Lunetta, KL; Ma, YY; Macias, J; Macleod, CA; Maier, W; Mangialasche, F; Spallazzi, M; Marquie, M; Marshall, R; Martin, ER; Montes, AM; Rodriguez, CM; Masullo, C; Mayeux, R; Mead, S; Mecocci, P; Medina, M; Meggy, A; Mehrabian, S; Mendoza, S; Menendez-Gonzale ...; Mir, P; Moebus, S; Mol, M; Molina-Porcel, L; Montrreal, L; Morelli, L; Moreno, F; Morgan, K; Mosley, T; Nothen, MM; Muchnik, C; Mukherjee, S; Nacmias, B; Ngandu, T; Nicolas, G; Nordestgaard, BG; Olaso, R; Orellana, A; Orsini, M; Ortega, G; Padovani, A; Paolo, C; Papenberg, G; Parnetti, L; Pasquier, F; Pastor, P; Peloso, G; Perez-Cordon, A; Perez-Tur, J; Pericard, P; Peters, O; Pijnenburg, YAL; Pineda, JA; Pinol-Ripoll, G; Pisanu, L; Polak, T; Popp, J; Posthuma, D; Priller, J; Puerta, R; Quenez, O; Quintela, I; Thomassen, JQ; Rabano, A; Rainero, I; Rajabli, F; Ramakers, I; Real, LM; Reinders, MJT; Reitz, C; Reyes-Dumeyer, D; Ridge, P; Riedel-Heller, S; Riederer, P; Roberto, N; Rodriguez-Rodrig ...; Rongve, A; Allende, IR; Rosende-Roca, M; Royo, JL; Rubino, E; Rujescu, D; Saez, ME; Sakka, P; Saltvedt, I; Sanchez-Arjona, ...; Sanchez-Garcia, ...; Juan, PS; Sanchez-Valle, R; Sando, SB; Sarnowski, C; Satizabal, CL; Scamosci, M; Scarmeas, N; Scarpini, E; Scheltens, P; Scherbaum, N; Scherer, M; Schmid, M; Schneider, A; Schott, JM; Selbaek, G; Seripa, D; Serrano, M; Sha, J; Shadrin, AA; Skrobot, O; Slifer, S; Snijders, GJL; Soininen, H; Solfrizzi, V; Solomon, A; Song, Y; Sorbi, S; Sotolongo-Grau, ...; Spalletta, G; Spottke, A; Squassina, A; Stordal, E; Tartan, JP; Tarraga, L; Tesi, N; Thalamuthu, A; Thomas, T; Tosto, G; Traykov, L; Tremolizzo, L; Tybjaeg-Hansen, ...; Uitterlinden, A; Ullgren, A; Ulstein, I; Valero, S; Valladares, O; Van Broeckhoven, ...; Vance, J; Vardarajan, BN; van der Lugt, A; Van Dongen, J; van Rooij, J; van Swieten, J; Vandenberghe, R; Verhey, F; Vidal, JS; Vogelgsang, J; Vyhnalek, M; Wagner, M; Wallon, D; Wang, LS; Wang, RQ; Weinhold, L; Wiltfang, J; Windle, G; Woods, B; Yannakoulia, M; Zare, H; Zhao, Y; Zhang, XL; Zhu, CC; Zulaica, M; Farrer, LA; Psaty, BM; Ghanbari, M; Raj, T; Sachdev, P; Mather, K; Jessen, F; Ikram, MA; de Mendonca, A; Hort, J; Tsolaki, M; Pericak-Vance, M ...; Amouyel, P; Williams, J; Frikke-Schmidt, ...; Clarimon, J; Deleuze, JF; Rossi, G; Seshadri, S; Andreassen, OA; Ingelsson, Marti ...; Hiltunen, M; Sleegers, K; Schellenberg, GD; van Duijn, CM; Sims, R; van der Flier, W ...; Ruiz, A; Ramirez, A; Lambert, JC; show less...

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