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New insights into the genetic etiology of Alzheimer's disease and related dementias. / Bellenguez, Céline; Küçükali, 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; Alarcón-Martín, Emilio; Alcolea, Daniel; Alegret, Montserrat; Alvarez, Ignacio; Álvarez, Victoria; Armstrong, Nicola J.; Tsolaki, Anthoula; Antúnez, Carmen; Appollonio, Ildebrando; Arcaro, Marina; Archetti, Silvana; Pastor, Alfonso Arias; Arosio, Beatrice; Athanasiu, Lavinia; Bailly, Henri; Banaj, Nerisa; Baquero, Miquel; Barral, Sandra; Beiser, Alexa; Nielsen, Sune Fallgaard; Nordestgaard, Børge G.; Sáez, María Eugenia; Frikke-Schmidt, Ruth; EADB; GR@ACE; DEGESCO; EADI; GERAD; Demgene; FinnGen; ADGC; CHARGE.
In:
Nature Genetics, Vol. 54, No. 4, 2022, p. 412-436.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Bellenguez, C, Küçükali, F, Jansen, IE, Kleineidam, L, Moreno-Grau, S, Amin, N, 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, V, Aarsland, D, Garcia-Gonzalez, P, Abdelnour, C, Alarcón-Martín, E, Alcolea, D, Alegret, M, Alvarez, I, Álvarez, V, Armstrong, NJ, Tsolaki, A, Antúnez, C, Appollonio, I, Arcaro, M, Archetti, S, Pastor, AA, Arosio, B, Athanasiu, L, Bailly, H, Banaj, N, Baquero, M, Barral, S, Beiser, A, Nielsen, SF
, Nordestgaard, BG, Sáez, ME
, Frikke-Schmidt, R, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC & CHARGE 2022, '
New insights into the genetic etiology of Alzheimer's disease and related dementias',
Nature Genetics, vol. 54, no. 4, pp. 412-436.
https://doi.org/10.1038/s41588-022-01024-zAPA
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., ... CHARGE (2022).
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Nature Genetics,
54(4), 412-436.
https://doi.org/10.1038/s41588-022-01024-zVancouver
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N et al.
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Nature Genetics. 2022;54(4):412-436.
https://doi.org/10.1038/s41588-022-01024-zAuthor
Bellenguez, Céline ; Küçükali, 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 ; Alarcón-Martín, Emilio ; Alcolea, Daniel ; Alegret, Montserrat ; Alvarez, Ignacio ; Álvarez, Victoria ; Armstrong, Nicola J. ; Tsolaki, Anthoula ; Antúnez, Carmen ; Appollonio, Ildebrando ; Arcaro, Marina ; Archetti, Silvana ; Pastor, Alfonso Arias ; Arosio, Beatrice ; Athanasiu, Lavinia ; Bailly, Henri ; Banaj, Nerisa ; Baquero, Miquel ; Barral, Sandra ; Beiser, Alexa ; Nielsen, Sune Fallgaard ; Nordestgaard, Børge G. ; Sáez, María Eugenia ; Frikke-Schmidt, Ruth ; EADB ; GR@ACE ; DEGESCO ; EADI ; GERAD ; Demgene ; FinnGen ; ADGC ; CHARGE. / New insights into the genetic etiology of Alzheimer's disease and related dementias. In: Nature Genetics. 2022 ; Vol. 54, No. 4. pp. 412-436.
Bibtex
@article{596c5d3136e74c79b259392ac4a08be8,
title = "New insights into the genetic etiology of Alzheimer's disease and related dementias",
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.",
author = "C{\'e}line Bellenguez and Fahri K{\"u}{\c c}{\"u}kali and Jansen, {Iris E.} and Luca Kleineidam and Sonia Moreno-Grau and Najaf Amin and Naj, {Adam C.} and Rafael Campos-Martin and Benjamin Grenier-Boley and Victor Andrade and Holmans, {Peter A.} and Anne Boland and Vincent Damotte and {van der Lee}, {Sven J.} and Costa, {Marcos R.} and Teemu Kuulasmaa and Qiong Yang and {de Rojas}, Itziar and Bis, {Joshua C.} and Amber Yaqub and Ivana Prokic and Julien Chapuis and Shahzad Ahmad and Vilmantas Giedraitis and Dag Aarsland and Pablo Garcia-Gonzalez and Carla Abdelnour and Emilio Alarc{\'o}n-Mart{\'i}n and Daniel Alcolea and Montserrat Alegret and Ignacio Alvarez and Victoria {\'A}lvarez and Armstrong, {Nicola J.} and Anthoula Tsolaki and Carmen Ant{\'u}nez and Ildebrando Appollonio and Marina Arcaro and Silvana Archetti and Pastor, {Alfonso Arias} and Beatrice Arosio and Lavinia Athanasiu and Henri Bailly and Nerisa Banaj and Miquel Baquero and Sandra Barral and Alexa Beiser and Nielsen, {Sune Fallgaard} and Nordestgaard, {B{\o}rge G.} and S{\'a}ez, {Mar{\'i}a Eugenia} and Ruth Frikke-Schmidt and EADB and GR@ACE and DEGESCO and EADI and GERAD and Demgene and FinnGen and ADGC and CHARGE",
note = "Publisher Copyright: {\textcopyright} 2022. The Author(s).",
year = "2022",
doi = "10.1038/s41588-022-01024-z",
language = "English",
volume = "54",
pages = "412--436",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "4",
}
RIS
TY - JOUR
T1 - New insights into the genetic etiology of Alzheimer's disease and related dementias
AU - Bellenguez, Céline
AU - Küçükali, Fahri
AU - Jansen, Iris E.
AU - Kleineidam, Luca
AU - Moreno-Grau, Sonia
AU - Amin, Najaf
AU - Naj, Adam C.
AU - Campos-Martin, Rafael
AU - Grenier-Boley, Benjamin
AU - Andrade, Victor
AU - Holmans, Peter A.
AU - Boland, Anne
AU - Damotte, Vincent
AU - van der Lee, Sven J.
AU - Costa, Marcos R.
AU - Kuulasmaa, Teemu
AU - Yang, Qiong
AU - de Rojas, Itziar
AU - Bis, Joshua C.
AU - Yaqub, Amber
AU - Prokic, Ivana
AU - Chapuis, Julien
AU - Ahmad, Shahzad
AU - Giedraitis, Vilmantas
AU - Aarsland, Dag
AU - Garcia-Gonzalez, Pablo
AU - Abdelnour, Carla
AU - Alarcón-Martín, Emilio
AU - Alcolea, Daniel
AU - Alegret, Montserrat
AU - Alvarez, Ignacio
AU - Álvarez, Victoria
AU - Armstrong, Nicola J.
AU - Tsolaki, Anthoula
AU - Antúnez, Carmen
AU - Appollonio, Ildebrando
AU - Arcaro, Marina
AU - Archetti, Silvana
AU - Pastor, Alfonso Arias
AU - Arosio, Beatrice
AU - Athanasiu, Lavinia
AU - Bailly, Henri
AU - Banaj, Nerisa
AU - Baquero, Miquel
AU - Barral, Sandra
AU - Beiser, Alexa
AU - Nielsen, Sune Fallgaard
AU - Nordestgaard, Børge G.
AU - Sáez, María Eugenia
AU - Frikke-Schmidt, Ruth
AU - EADB
AU - GR@ACE
AU - DEGESCO
AU - EADI
AU - GERAD
AU - Demgene
AU - FinnGen
AU - ADGC
AU - CHARGE
N1 - Publisher Copyright:
© 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-022-01024-z
DO - 10.1038/s41588-022-01024-z
M3 - Journal article
C2 - 35379992
AN - SCOPUS:85128487295
VL - 54
SP - 412
EP - 436
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 4
ER -
