New insights into the genetic etiology of Alzheimer's disease and related dementias.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
16
06
2021
accepted:
27
01
2022
pubmed:
6
4
2022
medline:
15
4
2022
entrez:
5
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35379992
doi: 10.1038/s41588-022-01024-z
pii: 10.1038/s41588-022-01024-z
pmc: PMC9005347
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
412-436Subventions
Organisme : NHLBI NIH HHS
ID : N01HC55222
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG053760
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066444
Pays : United States
Organisme : NIA NIH HHS
ID : K08 AG065463
Pays : United States
Organisme : Medical Research Council
ID : MR/R024804/1
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001445
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Organisme : Medical Research Council
ID : G0801418/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17112
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG022374
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL103612
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG057191
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006375
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058654
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS017950
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036528
Pays : United States
Organisme : Medical Research Council
ID : MR/L023784/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG054005
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028377
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0902227
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG054076
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005142
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059421
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG035137
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062622
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG009029
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005131
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG031581
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG009956
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL080295
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066511
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG072122
Pays : United States
Organisme : NEI NIH HHS
ID : T32 EY007157
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017586
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061356
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG066849
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036650
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG019085
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008657
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG055824
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG013616
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030146
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIMHD NIH HHS
ID : P20 MD000546
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00006
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG017173
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029893
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS039764
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003991
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013846
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG056270
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036502
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG026276
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072980
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087652
Pays : United States
Organisme : Medical Research Council
ID : MR/L501517/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0601022
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : Medical Research Council
ID : MR/K013041/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG028786
Pays : United States
Organisme : NCRR NIH HHS
ID : KL2 RR024151
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG049607
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG012300
Pays : United States
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R21 AG063130
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059319
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037985
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG024904
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NIA NIH HHS
ID : F99 AG073565
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG012101
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023651
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK066134
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016570
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85083
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008017
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG042437
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG041689
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Organisme : Medical Research Council
ID : MR/L501529/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066530
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036042
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058589
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG026395
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG015473
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : Medical Research Council
ID : G0300429
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005133
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066509
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States
Organisme : NIA NIH HHS
ID : RC2 AG036547
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG002219
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006781
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041797
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005144
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG010491
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066546
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033040
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : Medical Research Council
ID : UKDRI-2002
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG048927
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057473
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037212
Pays : United States
Organisme : Motor Neurone Disease Association
ID : ALCHALABI-DOBSON/APR14/829-791
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG052409
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG068880
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG021547
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041232
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG019757
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG020688
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG022018
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072977
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG020098
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118146
Pays : United States
Organisme : Medical Research Council
ID : G9901400
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030653
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027944
Pays : United States
Organisme : NINDS NIH HHS
ID : UH2 NS100605
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061872
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG025259
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003949
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057519
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004610
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072976
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010129
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG011101
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016582
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048015
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG041718
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025711
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061351
Pays : United States
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG072972
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023629
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066514
Pays : United States
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017216
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG033514
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS059873
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG068753
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG036836
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072979
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG026916
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG049505
Pays : United States
Investigateurs
Jan Laczo
(J)
Vaclav Matoska
(V)
Maria Serpente
(M)
Francesca Assogna
(F)
Fabrizio Piras
(F)
Federica Piras
(F)
Valentina Ciullo
(V)
Jacob Shofany
(J)
Carlo Ferrarese
(C)
Simona Andreoni
(S)
Gessica Sala
(G)
Chiara Paola Zoia
(CP)
Maria Del Zompo
(MD)
Alberto Benussi
(A)
Patrizia Bastiani
(P)
Mari Takalo
(M)
Teemu Natunen
(T)
Tiina Laatikainen
(T)
Jaakko Tuomilehto
(J)
Riitta Antikainen
(R)
Timo Strandberg
(T)
Jaana Lindström
(J)
Markku Peltonen
(M)
Richard Abraham
(R)
Ammar Al-Chalabi
(A)
Nicholas J Bass
(NJ)
Carol Brayne
(C)
Kristelle S Brown
(KS)
John Collinge
(J)
David Craig
(D)
Pangiotis Deloukas
(P)
Nick Fox
(N)
Amy Gerrish
(A)
Michael Gill
(M)
Rhian Gwilliam
(R)
Denise Harold
(D)
Paul Hollingworth
(P)
Jarret A Johnston
(JA)
Lesley Jones
(L)
Brian Lawlor
(B)
Gill Livingston
(G)
Simon Lovestone
(S)
Michelle Lupton
(M)
Aoibhinn Lynch
(A)
David Mann
(D)
Bernadette McGuinness
(B)
Andrew McQuillin
(A)
Michael C O'Donovan
(MC)
Michael J Owen
(MJ)
Peter Passmore
(P)
John F Powell
(JF)
Petra Proitsi
(P)
Martin Rossor
(M)
Christopher E Shaw
(CE)
A David Smith
(AD)
Hugh Gurling
(H)
Stephen Todd
(S)
Catherine Mummery
(C)
Nathalie Ryan
(N)
Giordano Lacidogna
(G)
Ad Adarmes-Gómez
(A)
Ana Mauleón
(A)
Ana Pancho
(A)
Anna Gailhajenet
(A)
Asunción Lafuente
(A)
D Macias-García
(D)
Elvira Martín
(E)
Esther Pelejà
(E)
F Carrillo
(F)
Isabel Sastre Merlín
(IS)
L Garrote-Espina
(L)
Liliana Vargas
(L)
M Carrion-Claro
(M)
M Marín
(M)
Ma Labrador
(M)
Mar Buendia
(M)
María Dolores Alonso
(MD)
Marina Guitart
(M)
Mariona Moreno
(M)
Marta Ibarria
(M)
Mt Periñán
(M)
Nuria Aguilera
(N)
P Gómez-Garre
(P)
Pilar Cañabate
(P)
R Escuela
(R)
R Pineda-Sánchez
(R)
R Vigo-Ortega
(R)
S Jesús
(S)
Silvia Preckler
(S)
Silvia Rodrigo-Herrero
(S)
Susana Diego
(S)
Alessandro Vacca
(A)
Fausto Roveta
(F)
Nicola Salvadori
(N)
Elena Chipi
(E)
Henning Boecker
(H)
Christoph Laske
(C)
Robert Perneczky
(R)
Costas Anastasiou
(C)
Daniel Janowitz
(D)
Rainer Malik
(R)
Anna Anastasiou
(A)
Kayenat Parveen
(K)
Carmen Lage
(C)
Sara López-García
(S)
Anna Antonell
(A)
Kalina Yonkova Mihova
(KY)
Diyana Belezhanska
(D)
Heike Weber
(H)
Silvia Kochen
(S)
Patricia Solis
(P)
Nancy Medel
(N)
Julieta Lisso
(J)
Zulma Sevillano
(Z)
Daniel G Politis
(DG)
Valeria Cores
(V)
Carolina Cuesta
(C)
Cecilia Ortiz
(C)
Juan Ignacio Bacha
(JI)
Mario Rios
(M)
Aldo Saenz
(A)
Mariana Sanchez Abalos
(MS)
Eduardo Kohler
(E)
Dana Lis Palacio
(DL)
Ignacio Etchepareborda
(I)
Matias Kohler
(M)
Gisela Novack
(G)
Federico Ariel Prestia
(FA)
Pablo Galeano
(P)
Eduardo M Castaño
(EM)
Sandra Germani
(S)
Carlos Reyes Toso
(CR)
Matias Rojo
(M)
Carlos Ingino
(C)
Carlos Mangone
(C)
David C Rubinsztein
(DC)
Stefan Teipel
(S)
Nathalie Fievet
(N)
Vincent Deramerourt
(V)
Charlotte Forsell
(C)
Håkan Thonberg
(H)
Maria Bjerke
(M)
Ellen De Roeck
(E)
María Teresa Martínez-Larrad
(MT)
Natividad Olivar
(N)
Nuria Aguilera
(N)
Amanda Cano
(A)
Pilar Cañabate
(P)
Juan Macias
(J)
Olalla Maroñas
(O)
Raúl Nuñez-Llaves
(R)
Clàudia Olivé
(C)
Ester Pelejá
(E)
Astrid D Adarmes-Gómez
(AD)
María Dolores Alonso
(MD)
Guillermo Amer-Ferrer
(G)
Martirio Antequera
(M)
Juan Andrés Burguera
(JA)
Fátima Carrillo
(F)
Mario Carrión-Claro
(M)
María José Casajeros
(MJ)
Marian Martinez de Pancorbo
(M)
Rocío Escuela
(R)
Lorena Garrote-Espina
(L)
Pilar Gómez-Garre
(P)
Saray Hevilla
(S)
Silvia Jesús
(S)
Miguel Angel Labrador Espinosa
(MAL)
Agustina Legaz
(A)
Sara López-García
(S)
Daniel Macias-García
(D)
Salvadora Manzanares
(S)
Marta Marín
(M)
Juan Marín-Muñoz
(J)
Tamara Marín
(T)
Begoña Martínez
(B)
Victoriana Martínez
(V)
Pablo Martínez-Lage Álvarez
(P)
Maite Mendioroz Iriarte
(MM)
María Teresa Periñán-Tocino
(MT)
Rocío Pineda-Sánchez
(R)
Diego Real de Asúa
(D)
Silvia Rodrigo
(S)
Isabel Sastre
(I)
Maria Pilar Vicente
(MP)
Rosario Vigo-Ortega
(R)
Liliana Vivancos
(L)
Jacques Epelbaum
(J)
Didier Hannequin
(D)
Dominique Campion
(D)
Vincent Deramecourt
(V)
Christophe Tzourio
(C)
Alexis Brice
(A)
Bruno Dubois
(B)
Amy Williams
(A)
Charlene Thomas
(C)
Chloe Davies
(C)
William Nash
(W)
Kimberley Dowzell
(K)
Atahualpa Castillo Morales
(AC)
Mateus Bernardo-Harrington
(M)
James Turton
(J)
Jenny Lord
(J)
Kristelle Brown
(K)
Emma Vardy
(E)
Elizabeth Fisher
(E)
Jason D Warren
(JD)
Martin Rossor
(M)
Natalie S Ryan
(NS)
Rita Guerreiro
(R)
James Uphill
(J)
Nick Bass
(N)
Reinhard Heun
(R)
Heike Kölsch
(H)
Britta Schürmann
(B)
André Lacour
(A)
Christine Herold
(C)
Janet A Johnston
(JA)
Peter Passmore
(P)
John Powell
(J)
Yogen Patel
(Y)
Angela Hodges
(A)
Tim Becker
(T)
Donald Warden
(D)
Gordon Wilcock
(G)
Robert Clarke
(R)
Panagiotis Deloukas
(P)
Yoav Ben-Shlomo
(Y)
Nigel M Hooper
(NM)
Stuart Pickering-Brown
(S)
Rebecca Sussams
(R)
Nick Warner
(N)
Anthony Bayer
(A)
Isabella Heuser
(I)
Dmitriy Drichel
(D)
Norman Klopp
(N)
Manuel Mayhaus
(M)
Matthias Riemenschneider
(M)
Sabrina Pinchler
(S)
Thomas Feulner
(T)
Wei Gu
(W)
Hendrik van den Bussche
(H)
Michael Hüll
(M)
Lutz Frölich
(L)
H-Erich Wichmann
(HE)
Karl-Heinz Jöckel
(KH)
Michael O'Donovan
(M)
Michael Owen
(M)
Shahram Bahrami
(S)
Ingunn Bosnes
(I)
Per Selnes
(P)
Sverre Bergh
(S)
Aarno Palotie
(A)
Mark Daly
(M)
Howard Jacob
(H)
Athena Matakidou
(A)
Heiko Runz
(H)
Sally John
(S)
Robert Plenge
(R)
Mark McCarthy
(M)
Julie Hunkapiller
(J)
Meg Ehm
(M)
Dawn Waterworth
(D)
Caroline Fox
(C)
Anders Malarstig
(A)
Kathy Klinger
(K)
Kathy Call
(K)
Tim Behrens
(T)
Patrick Loerch
(P)
Tomi Mäkelä
(T)
Jaakko Kaprio
(J)
Petri Virolainen
(P)
Kari Pulkki
(K)
Terhi Kilpi
(T)
Markus Perola
(M)
Jukka Partanen
(J)
Anne Pitkäranta
(A)
Riitta Kaarteenaho
(R)
Seppo Vainio
(S)
Miia Turpeinen
(M)
Raisa Serpi
(R)
Tarja Laitinen
(T)
Johanna Mäkelä
(J)
Veli-Matti Kosma
(VM)
Urho Kujala
(U)
Outi Tuovila
(O)
Minna Hendolin
(M)
Raimo Pakkanen
(R)
Jeff Waring
(J)
Bridget Riley-Gillis
(B)
Jimmy Liu
(J)
Shameek Biswas
(S)
Dorothee Diogo
(D)
Catherine Marshall
(C)
Xinli Hu
(X)
Matthias Gossel
(M)
Robert Graham
(R)
Beryl Cummings
(B)
Samuli Ripatti
(S)
Johanna Schleutker
(J)
Mikko Arvas
(M)
Olli Carpén
(O)
Reetta Hinttala
(R)
Johannes Kettunen
(J)
Arto Mannermaa
(A)
Jari Laukkanen
(J)
Valtteri Julkunen
(V)
Anne Remes
(A)
Reetta Kälviäinen
(R)
Jukka Peltola
(J)
Pentti Tienari
(P)
Juha Rinne
(J)
Adam Ziemann
(A)
Jeffrey Waring
(J)
Sahar Esmaeeli
(S)
Nizar Smaoui
(N)
Anne Lehtonen
(A)
Susan Eaton
(S)
Sanni Lahdenperä
(S)
Janet van Adelsberg
(J)
John Michon
(J)
Geoff Kerchner
(G)
Natalie Bowers
(N)
Edmond Teng
(E)
John Eicher
(J)
Vinay Mehta
(V)
Padhraig Gormley
(P)
Kari Linden
(K)
Christopher Whelan
(C)
Fanli Xu
(F)
David Pulford
(D)
Martti Färkkilä
(M)
Sampsa Pikkarainen
(S)
Airi Jussila
(A)
Timo Blomster
(T)
Mikko Kiviniemi
(M)
Markku Voutilainen
(M)
Bob Georgantas
(B)
Graham Heap
(G)
Fedik Rahimov
(F)
Keith Usiskin
(K)
Tim Lu
(T)
Danny Oh
(D)
Kirsi Kalpala
(K)
Melissa Miller
(M)
Linda McCarthy
(L)
Kari Eklund
(K)
Antti Palomäki
(A)
Pia Isomäki
(P)
Laura Pirilä
(L)
Oili Kaipiainen-Seppänen
(O)
Johanna Huhtakangas
(J)
Apinya Lertratanakul
(A)
Marla Hochfeld
(M)
Nan Bing
(N)
Jorge Esparza Gordillo
(JE)
Nina Mars
(N)
Margit Pelkonen
(M)
Paula Kauppi
(P)
Hannu Kankaanranta
(H)
Terttu Harju
(T)
David Close
(D)
Steven Greenberg
(S)
Hubert Chen
(H)
Jo Betts
(J)
Soumitra Ghosh
(S)
Veikko Salomaa
(V)
Teemu Niiranen
(T)
Markus Juonala
(M)
Kaj Metsärinne
(K)
Mika Kähönen
(M)
Juhani Junttila
(J)
Markku Laakso
(M)
Jussi Pihlajamäki
(J)
Juha Sinisalo
(J)
Marja-Riitta Taskinen
(MR)
Tiinamaija Tuomi
(T)
Ben Challis
(B)
Andrew Peterson
(A)
Audrey Chu
(A)
Jaakko Parkkinen
(J)
Anthony Muslin
(A)
Heikki Joensuu
(H)
Tuomo Meretoja
(T)
Lauri Aaltonen
(L)
Johanna Mattson
(J)
Annika Auranen
(A)
Peeter Karihtala
(P)
Saila Kauppila
(S)
Päivi Auvinen
(P)
Klaus Elenius
(K)
Relja Popovic
(R)
Jennifer Schutzman
(J)
Andrey Loboda
(A)
Aparna Chhibber
(A)
Heli Lehtonen
(H)
Stefan McDonough
(S)
Marika Crohns
(M)
Diptee Kulkarni
(D)
Kai Kaarniranta
(K)
Joni A Turunen
(JA)
Terhi Ollila
(T)
Sanna Seitsonen
(S)
Hannu Uusitalo
(H)
Vesa Aaltonen
(V)
Hannele Uusitalo-Järvinen
(H)
Marja Luodonpää
(M)
Nina Hautala
(N)
Stephanie Loomis
(S)
Erich Strauss
(E)
Hao Chen
(H)
Anna Podgornaia
(A)
Joshua Hoffman
(J)
Kaisa Tasanen
(K)
Laura Huilaja
(L)
Katariina Hannula-Jouppi
(K)
Teea Salmi
(T)
Sirkku Peltonen
(S)
Leena Koulu
(L)
Ilkka Harvima
(I)
Ying Wu
(Y)
David Choy
(D)
Pirkko Pussinen
(P)
Aino Salminen
(A)
Tuula Salo
(T)
David Rice
(D)
Pekka Nieminen
(P)
Ulla Palotie
(U)
Maria Siponen
(M)
Liisa Suominen
(L)
Päivi Mäntylä
(P)
Ulvi Gursoy
(U)
Vuokko Anttonen
(V)
Kirsi Sipilä
(K)
Justin Wade Davis
(JW)
Danjuma Quarless
(D)
Slavé Petrovski
(S)
Eleonor Wigmore
(E)
Chia-Yen Chen
(CY)
Paola Bronson
(P)
Ellen Tsai
(E)
Yunfeng Huang
(Y)
Joseph Maranville
(J)
Elmutaz Shaikho
(E)
Elhaj Mohammed
(E)
Samir Wadhawan
(S)
Erika Kvikstad
(E)
Minal Caliskan
(M)
Diana Chang
(D)
Tushar Bhangale
(T)
Sarah Pendergrass
(S)
Emily Holzinger
(E)
Xing Chen
(X)
Åsa Hedman
(Å)
Karen S King
(KS)
Clarence Wang
(C)
Ethan Xu
(E)
Franck Auge
(F)
Clement Chatelain
(C)
Deepak Rajpal
(D)
Dongyu Liu
(D)
Katherine Call
(K)
Tai-He Xia
(TH)
Matt Brauer
(M)
Mitja Kurki
(M)
Juha Karjalainen
(J)
Aki Havulinna
(A)
Anu Jalanko
(A)
Priit Palta
(P)
Pietro Della Briotta Parolo
(P)
Wei Zhou
(W)
Susanna Lemmelä
(S)
Manuel Rivas
(M)
Jarmo Harju
(J)
Arto Lehisto
(A)
Andrea Ganna
(A)
Vincent Llorens
(V)
Hannele Laivuori
(H)
Sina Rüeger
(S)
Mari E Niemi
(ME)
Taru Tukiainen
(T)
Mary Pat Reeve
(MP)
Henrike Heyne
(H)
Kimmo Palin
(K)
Javier Garcia-Tabuenca
(J)
Harri Siirtola
(H)
Tuomo Kiiskinen
(T)
Jiwoo Lee
(J)
Kristin Tsuo
(K)
Amanda Elliott
(A)
Kati Kristiansson
(K)
Kati Hyvärinen
(K)
Jarmo Ritari
(J)
Miika Koskinen
(M)
Katri Pylkäs
(K)
Marita Kalaoja
(M)
Minna Karjalainen
(M)
Tuomo Mantere
(T)
Eeva Kangasniemi
(E)
Sami Heikkinen
(S)
Eija Laakkonen
(E)
Csilla Sipeky
(C)
Samuel Heron
(S)
Antti Karlsson
(A)
Dhanaprakash Jambulingam
(D)
Venkat Subramaniam Rathinakannan
(VS)
Risto Kajanne
(R)
Mervi Aavikko
(M)
Manuel González Jiménez
(MG)
Pietro Della Briotta Parola
(P)
Arto Lehistö
(A)
Masahiro Kanai
(M)
Mari Kaunisto
(M)
Elina Kilpeläinen
(E)
Timo P Sipilä
(TP)
Georg Brein
(G)
Ghazal Awaisa
(G)
Anastasia Shcherban
(A)
Kati Donner
(K)
Anu Loukola
(A)
Päivi Laiho
(P)
Tuuli Sistonen
(T)
Essi Kaiharju
(E)
Markku Laukkanen
(M)
Elina Järvensivu
(E)
Sini Lähteenmäki
(S)
Lotta Männikkö
(L)
Regis Wong
(R)
Hannele Mattsson
(H)
Tero Hiekkalinna
(T)
Teemu Paajanen
(T)
Kalle Pärn
(K)
Javier Gracia-Tabuenca
(J)
Erin Abner
(E)
Perrie M Adams
(PM)
Alyssa Aguirre
(A)
Marilyn S Albert
(MS)
Roger L Albin
(RL)
Mariet Allen
(M)
Lisa Alvarez
(L)
Liana G Apostolova
(LG)
Steven E Arnold
(SE)
Sanjay Asthana
(S)
Craig S Atwood
(CS)
Gayle Ayres
(G)
Clinton T Baldwin
(CT)
Robert C Barber
(RC)
Lisa L Barnes
(LL)
Sandra Barral
(S)
Thomas G Beach
(TG)
James T Becker
(JT)
Gary W Beecham
(GW)
Duane Beekly
(D)
Jennifer E Below
(JE)
Penelope Benchek
(P)
Bruno A Benitez
(BA)
David Bennett
(D)
John Bertelson
(J)
Flanagan E Margaret
(FE)
Thomas D Bird
(TD)
Deborah Blacker
(D)
Bradley F Boeve
(BF)
James D Bowen
(JD)
Adam Boxer
(A)
James Brewer
(J)
James R Burke
(JR)
Jeffrey M Burns
(JM)
Will S Bush
(WS)
Joseph D Buxbaum
(JD)
Nigel J Cairns
(NJ)
Chuanhai Cao
(C)
Christopher S Carlson
(CS)
Cynthia M Carlsson
(CM)
Regina M Carney
(RM)
Minerva M Carrasquillo
(MM)
Scott Chasse
(S)
Marie-Francoise Chesselet
(MF)
Alessandra Chesi
(A)
Nathaniel A Chin
(NA)
Helena C Chui
(HC)
Jaeyoon Chung
(J)
Suzanne Craft
(S)
Paul K Crane
(PK)
David H Cribbs
(DH)
Elizabeth A Crocco
(EA)
Carlos Cruchaga
(C)
Michael L Cuccaro
(ML)
Munro Cullum
(M)
Eveleen Darby
(E)
Barbara Davis
(B)
Philip L De Jager
(PL)
Charles DeCarli
(C)
John DeToledo
(J)
Malcolm Dick
(M)
Dennis W Dickson
(DW)
Beth A Dombroski
(BA)
Rachelle S Doody
(RS)
Ranjan Duara
(R)
Nilüfer Ertekin-Taner
(N)
Denis A Evans
(DA)
Thomas J Fairchild
(TJ)
Kenneth B Fallon
(KB)
Martin R Farlow
(MR)
John J Farrell
(JJ)
Victoria Fernandez-Hernandez
(V)
Steven Ferris
(S)
Matthew P Frosch
(MP)
Brian Fulton-Howard
(B)
Douglas R Galasko
(DR)
Adriana Gamboa
(A)
Marla Gearing
(M)
Daniel H Geschwind
(DH)
Bernardino Ghetti
(B)
John R Gilbert
(JR)
Thomas J Grabowski
(TJ)
Neill R Graff-Radford
(NR)
Struan F A Grant
(SFA)
Robert C Green
(RC)
John H Growdon
(JH)
Jonathan L Haines
(JL)
Hakon Hakonarson
(H)
James Hall
(J)
Ronald L Hamilton
(RL)
Oscar Harari
(O)
Lindy E Harrell
(LE)
Jacob Haut
(J)
Elizabeth Head
(E)
Victor W Henderson
(VW)
Michelle Hernandez
(M)
Timothy Hohman
(T)
Lawrence S Honig
(LS)
Ryan M Huebinger
(RM)
Matthew J Huentelman
(MJ)
Christine M Hulette
(CM)
Bradley T Hyman
(BT)
Linda S Hynan
(LS)
Laura Ibanez
(L)
Gail P Jarvik
(GP)
Suman Jayadev
(S)
Lee-Way Jin
(LW)
Kim Johnson
(K)
Leigh Johnson
(L)
M Ilyas Kamboh
(MI)
Anna M Karydas
(AM)
Mindy J Katz
(MJ)
Jeffrey A Kaye
(JA)
C Dirk Keene
(CD)
Aisha Khaleeq
(A)
Ronald Kim
(R)
Janice Knebl
(J)
Neil W Kowall
(NW)
Joel H Kramer
(JH)
Pavel P Kuksa
(PP)
Frank M LaFerla
(FM)
James J Lah
(JJ)
Eric B Larson
(EB)
Chien-Yueh Lee
(CY)
Edward B Lee
(EB)
Alan Lerner
(A)
Yuk Yee Leung
(YY)
James B Leverenz
(JB)
Allan I Levey
(AI)
Mingyao Li
(M)
Andrew P Lieberman
(AP)
Richard B Lipton
(RB)
Mark Logue
(M)
Constantine G Lyketsos
(CG)
John Malamon
(J)
Douglas Mains
(D)
Daniel C Marson
(DC)
Frank Martiniuk
(F)
Deborah C Mash
(DC)
Eliezer Masliah
(E)
Paul Massman
(P)
Arjun Masurkar
(A)
Wayne C McCormick
(WC)
Susan M McCurry
(SM)
Andrew N McDavid
(AN)
Stefan McDonough
(S)
Ann C McKee
(AC)
Marsel Mesulam
(M)
Jesse Mez
(J)
Bruce L Miller
(BL)
Carol A Miller
(CA)
Joshua W Miller
(JW)
Thomas J Montine
(TJ)
Edwin S Monuki
(ES)
John C Morris
(JC)
Amanda J Myers
(AJ)
Trung Nguyen
(T)
Sid O'Bryant
(S)
John M Olichney
(JM)
Marcia Ory
(M)
Raymond Palmer
(R)
Joseph E Parisi
(JE)
Henry L Paulson
(HL)
Valory Pavlik
(V)
David Paydarfar
(D)
Victoria Perez
(V)
Elaine Peskind
(E)
Ronald C Petersen
(RC)
Jennifer E Phillips-Cremins
(JE)
Aimee Pierce
(A)
Marsha Polk
(M)
Wayne W Poon
(WW)
Huntington Potter
(H)
Liming Qu
(L)
Mary Quiceno
(M)
Joseph F Quinn
(JF)
Ashok Raj
(A)
Murray Raskind
(M)
Eric M Reiman
(EM)
Barry Reisberg
(B)
Joan S Reisch
(JS)
John M Ringman
(JM)
Erik D Roberson
(ED)
Monica Rodriguear
(M)
Ekaterina Rogaeva
(E)
Howard J Rosen
(HJ)
Roger N Rosenberg
(RN)
Donald R Royall
(DR)
Mark A Sager
(MA)
Mary Sano
(M)
Andrew J Saykin
(AJ)
Julie A Schneider
(JA)
Lon S Schneider
(LS)
William W Seeley
(WW)
Susan H Slifer
(SH)
Scott Small
(S)
Amanda G Smith
(AG)
Janet P Smith
(JP)
Yeunjoo E Song
(YE)
Joshua A Sonnen
(JA)
Salvatore Spina
(S)
Peter St George-Hyslop
(PS)
Robert A Stern
(RA)
Alan B Stevens
(AB)
Stephen M Strittmatter
(SM)
David Sultzer
(D)
Russell H Swerdlow
(RH)
Rudolph E Tanzi
(RE)
Jeffrey L Tilson
(JL)
John Q Trojanowski
(JQ)
Juan C Troncoso
(JC)
Debby W Tsuang
(DW)
Otto Valladares
(O)
Vivianna M Van Deerlin
(VM)
Linda J van Eldik
(LJ)
Robert Vassar
(R)
Harry V Vinters
(HV)
Jean-Paul Vonsattel
(JP)
Sandra Weintraub
(S)
Kathleen A Welsh-Bohmer
(KA)
Patrice L Whitehead
(PL)
Ellen M Wijsman
(EM)
Kirk C Wilhelmsen
(KC)
Benjamin Williams
(B)
Jennifer Williamson
(J)
Henrik Wilms
(H)
Thomas S Wingo
(TS)
Thomas Wisniewski
(T)
Randall L Woltjer
(RL)
Martin Woon
(M)
Clinton B Wright
(CB)
Chuang-Kuo Wu
(CK)
Steven G Younkin
(SG)
Chang-En Yu
(CE)
Lei Yu
(L)
Yuanchao Zhang
(Y)
Yi Zhao
(Y)
Xiongwei Zhu
(X)
Hieab Adams
(H)
Rufus O Akinyemi
(RO)
Muhammad Ali
(M)
Nicola Armstrong
(N)
Hugo J Aparicio
(HJ)
Maryam Bahadori
(M)
James T Becker
(JT)
Monique Breteler
(M)
Daniel Chasman
(D)
Ganesh Chauhan
(G)
Hata Comic
(H)
Simon Cox
(S)
Adrienne L Cupples
(AL)
Gail Davies
(G)
Charles S DeCarli
(CS)
Marie-Gabrielle Duperron
(MG)
Josée Dupuis
(J)
Tavia Evans
(T)
Frank Fan
(F)
Annette Fitzpatrick
(A)
Alison E Fohner
(AE)
Mary Ganguli
(M)
Mirjam Geerlings
(M)
Stephen J Glatt
(SJ)
Hector M Gonzalez
(HM)
Monica Goss
(M)
Hans Grabe
(H)
Mohamad Habes
(M)
Susan R Heckbert
(SR)
Edith Hofer
(E)
Elliot Hong
(E)
Timothy Hughes
(T)
Tiffany F Kautz
(TF)
Maria Knol
(M)
William Kremen
(W)
Paul Lacaze
(P)
Jari Lahti
(J)
Quentin Le Grand
(QL)
Elizabeth Litkowski
(E)
Shuo Li
(S)
Dan Liu
(D)
Xuan Liu
(X)
Marisa Loitfelder
(M)
Alisa Manning
(A)
Pauline Maillard
(P)
Riccardo Marioni
(R)
Bernard Mazoyer
(B)
Debora Melo van Lent
(DM)
Hao Mei
(H)
Aniket Mishra
(A)
Paul Nyquist
(P)
Jeffrey O'Connell
(J)
Yash Patel
(Y)
Tomas Paus
(T)
Zdenka Pausova
(Z)
Katri Raikkonen-Talvitie
(K)
Moeen Riaz
(M)
Stephen Rich
(S)
Jerome Rotter
(J)
Jose Romero
(J)
Gena Roshchupkin
(G)
Yasaman Saba
(Y)
Murali Sargurupremraj
(M)
Helena Schmidt
(H)
Reinhold Schmidt
(R)
Joshua M Shulman
(JM)
Jennifer Smith
(J)
Hema Sekhar
(H)
Reddy Rajula
(R)
Jean Shin
(J)
Jeannette Simino
(J)
Eeva Sliz
(E)
Alexander Teumer
(A)
Alvin Thomas
(A)
Adrienne Tin
(A)
Elliot Tucker-Drob
(E)
Dina Vojinovic
(D)
Yanbing Wang
(Y)
Galit Weinstein
(G)
Dylan Williams
(D)
Katharina Wittfeld
(K)
Lisa Yanek
(L)
Yunju Yang
(Y)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
Références
Gatz, M. et al. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63, 168–174 (2006).
pubmed: 16461860
doi: 10.1001/archpsyc.63.2.168
Bellenguez, C., Grenier-Boley, B. & Lambert, J. C. Genetics of Alzheimer’s disease: where we are, and where we are going. Curr. Opin. Neurobiol. 61, 40–48 (2020).
pubmed: 31863938
doi: 10.1016/j.conb.2019.11.024
Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. 51, 404–413 (2019).
pubmed: 30617256
pmcid: 6836675
doi: 10.1038/s41588-018-0311-9
Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).
pubmed: 25722852
pmcid: 4342193
doi: 10.1186/s13742-015-0047-8
Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 51, 414–430 (2019).
pubmed: 30820047
pmcid: 6463297
doi: 10.1038/s41588-019-0358-2
Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 45, 1452–1458 (2013).
pubmed: 24162737
pmcid: 3896259
doi: 10.1038/ng.2802
Liu, J. Z., Erlich, Y. & Pickrell, J. K. Case-control association mapping by proxy using family history of disease. Nat. Genet. 49, 325–331 (2017).
pubmed: 28092683
doi: 10.1038/ng.3766
Marioni, R. E. et al. GWAS on family history of Alzheimer’s disease. Transl. Psychiatry 8, 99 (2018).
pubmed: 29777097
pmcid: 5959890
doi: 10.1038/s41398-018-0150-6
Sims, R. et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease.Nat. Genet. 49, 1373–1384 (2017).
pubmed: 28714976
pmcid: 5669039
doi: 10.1038/ng.3916
Jun, G. et al. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol. Psychiatry 21, 108–117 (2016).
pubmed: 25778476
doi: 10.1038/mp.2015.23
Schwartzentruber, J. et al. Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer’s disease risk genes. Nat. Genet. 53, 392–402 (2021).
pubmed: 33589840
pmcid: 7610386
doi: 10.1038/s41588-020-00776-w
de Rojas, I. et al. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores. Nat. Commun. 12, 3417 (2021).
pubmed: 34099642
pmcid: 8184987
doi: 10.1038/s41467-021-22491-8
Wightman, D. P. et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease. Nat. Genet. 53, 1276–1282 (2021).
pubmed: 34493870
doi: 10.1038/s41588-021-00921-z
Skene, N. G. et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet. 50, 825–833 (2018).
pubmed: 29785013
pmcid: 6477180
doi: 10.1038/s41588-018-0129-5
de Leeuw, C. A., Stringer, S., Dekkers, I. A., Heskes, T. & Posthuma, D. Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure. Nat. Commun. 9, 3768 (2018).
pubmed: 30218068
pmcid: 6138636
doi: 10.1038/s41467-018-06022-6
Haass, C., Kaether, C., Thinakaran, G. & Sisodia, S. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med. 2, a006270 (2012).
pubmed: 22553493
pmcid: 3331683
doi: 10.1101/cshperspect.a006270
Chapuis, J. et al. Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism. Acta Neuropathol. 133, 955–966 (2017).
pubmed: 27933404
doi: 10.1007/s00401-016-1652-z
Cleynen, A. et al. Expressed fusion gene landscape and its impact in multiple myeloma. Nat. Commun. 8, 1893 (2017).
pubmed: 29196615
pmcid: 5711960
doi: 10.1038/s41467-017-00638-w
Szklarczyk, D. et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47, D607–D613 (2019).
pubmed: 30476243
doi: 10.1093/nar/gky1131
Spit, M., Rieser, E. & Walczak, H. Linear ubiquitination at a glance. J. Cell Sci. 132, jcs208512 (2019).
pubmed: 30659056
doi: 10.1242/jcs.208512
Pencina, M. J., D’Agostino, R. B., Pencina, K. M., Janssens, A. C. J. W. & Greenland, P. Interpreting incremental value of markers added to risk prediction models. Am. J. Epidemiol. 176, 473–481 (2012).
pubmed: 22875755
pmcid: 3530349
doi: 10.1093/aje/kws207
Dourlen, P., Chapuis, J. & Lambert, J.-C. Using high-throughput animal or cell-based models to functionally characterize GWAS signals. Curr. Genet. Med. Rep. 6, 107–115 (2018).
pubmed: 30147999
pmcid: 6096908
doi: 10.1007/s40142-018-0141-1
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J. & Lambert, J. C. The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? Acta Neuropathol. 138, 221–236 (2019).
pubmed: 30982098
pmcid: 6660578
doi: 10.1007/s00401-019-02004-0
Deuss, M., Reiss, K. & Hartmann, D. Part-time α-secretases: the functional biology of ADAM 9, 10 and 17. Curr. Alzheimer Res. 5, 187–201 (2008).
pubmed: 18393804
doi: 10.2174/156720508783954686
Kim, T. et al. Human LilrB2 is a β-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer’s model. Science 341, 1399–1404 (2013).
pubmed: 24052308
doi: 10.1126/science.1242077
Salminen, A. & Kaarniranta, K. Siglec receptors and hiding plaques in Alzheimer’s disease. J. Mol. Med. 87, 697–701 (2009).
pubmed: 19390836
doi: 10.1007/s00109-009-0472-1
Rodgers, M. A. et al. The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation. J. Exp. Med. 211, 1333–1347 (2014).
pubmed: 24958845
pmcid: 4076580
doi: 10.1084/jem.20132486
Iwai, K. LUBAC-mediated linear ubiquitination: a crucial regulator of immune signaling. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 97, 120–133 (2021).
pubmed: 33692228
pmcid: 8019854
doi: 10.2183/pjab.97.007
Venegas, C. et al. Microglia-derived ASC specks crossseed amyloid-β in Alzheimer’s disease. Nature 552, 355–361 (2017).
pubmed: 29293211
doi: 10.1038/nature25158
Ising, C. et al. NLRP3 inflammasome activation drives tau pathology. Nature 575, 669–673 (2019).
pubmed: 31748742
pmcid: 7324015
doi: 10.1038/s41586-019-1769-z
Nakayama, Y. et al. Linear polyubiquitin chain modification of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 79, 256–265 (2020).
pubmed: 31951008
doi: 10.1093/jnen/nlz135
Black, R. A. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-∅ from cells. Nature 385, 729–733 (1997).
pubmed: 9034190
doi: 10.1038/385729a0
Verstrepen, L., Carpentier, I., Verhelst, K. & Beyaert, R. ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling. Biochem. Pharmacol. 78, 105–114 (2009).
pubmed: 19464428
doi: 10.1016/j.bcp.2009.02.009
Spitz, C. et al. Non-canonical Shedding of TNFα by SPPL2a is determined by the conformational flexibility of its transmembrane helix. iScience 23, 101775 (2020).
pubmed: 33294784
pmcid: 7689174
doi: 10.1016/j.isci.2020.101775
Tang, W. et al. The growth factor progranulin binds to tnf receptors and is therapeutic against inflammatory arthritis in mice. Science 332, 478–484 (2011).
pubmed: 21393509
pmcid: 3104397
doi: 10.1126/science.1199214
He, P. et al. Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer’s mice. J. Cell Biol. 178, 829–841 (2007).
pubmed: 17724122
pmcid: 2064547
doi: 10.1083/jcb.200705042
Shi, J. Q. et al. Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res. 1368, 239–247 (2011).
pubmed: 20971085
doi: 10.1016/j.brainres.2010.10.053
Bezbradica, J. S., Coll, R. C. & Schroder, K. Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. Cell. Mol. Immunol. 14, 118–126 (2017).
pubmed: 26996064
doi: 10.1038/cmi.2016.11
Decourt, B., Lahiri, D. K. & Sabbagh, M. N. Targeting tumor necrosis factor alpha for Alzheimer’s disease. Curr. Alzheimer Res. 14, 412–425 (2016).
doi: 10.2174/1567205013666160930110551
De Strooper, B. & Karran, E. The cellular phase of Alzheimer’s disease. Cell 164, 603–615 (2016).
pubmed: 26871627
doi: 10.1016/j.cell.2015.12.056
Gong, K. et al. TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer. J. Clin. Invest. 128, 2500–2518 (2018).
pubmed: 29613856
pmcid: 5983340
doi: 10.1172/JCI96148
Rhinn, H. & Abeliovich, A. Differential aging analysis in human cerebral cortex identifies variants in TMEM106B and GRN that regulate aging phenotypes. Cell Syst. 4, 404–415 (2017).
pubmed: 28330615
doi: 10.1016/j.cels.2017.02.009
Vass, R. et al. Risk genotypes at TMEM106B are associated with cognitive impairment in amyotrophic lateral sclerosis. Acta Neuropathol. 121, 373–380 (2011).
pubmed: 21104415
doi: 10.1007/s00401-010-0782-y
Baizabal-Carvallo, J. F. & Jankovic, J. Parkinsonism, movement disorders and genetics in frontotemporal dementia. Nat. Rev. Neurol. 12, 175–185 (2016).
pubmed: 26891767
doi: 10.1038/nrneurol.2016.14
Tropea, T. F. et al. TMEM106B Effect on cognition in Parkinson disease and frontotemporal dementia. Ann. Neurol. 85, 801–811 (2019).
pubmed: 30973966
pmcid: 6953172
doi: 10.1002/ana.25486
Mendsaikhan, A., Tooyama, I. & Walker, D. G. Microglial progranulin: involvement in Alzheimer’s disease and neurodegenerative diseases. Cells 8, 230 (2019).
pmcid: 6468562
doi: 10.3390/cells8030230
Li, Z. et al. The TMEM106B FTLD-protective variant, rs1990621, is also associated with increased neuronal proportion. Acta Neuropathol. 139, 45–61 (2020).
pubmed: 31456032
doi: 10.1007/s00401-019-02066-0
Yang, H. S. et al. Genetics of gene expression in the aging human brain reveal TDP-43 proteinopathy pathophysiology. Neuron 107, 496–508.e6 (2020).
pubmed: 32526197
pmcid: 7416464
doi: 10.1016/j.neuron.2020.05.010
Paushter, D. H., Du, H., Feng, T. & Hu, F. The lysosomal function of progranulin, a guardian against neurodegeneration. Acta Neuropathol. 136, 1–17 (2018).
pubmed: 29744576
pmcid: 6117207
doi: 10.1007/s00401-018-1861-8
Feng, T., Lacrampe, A. & Hu, F. Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders. Acta Neuropathol. 141, 327–339 (2021).
pubmed: 33386471
pmcid: 8049516
doi: 10.1007/s00401-020-02246-3
Lacour, A. et al. Genome-wide significant risk factors for Alzheimer’s disease: role in progression to dementia due to Alzheimer’s disease among subjects with mild cognitive impairment. Mol. Psychiatry 22, 153–160 (2017).
pubmed: 26976043
doi: 10.1038/mp.2016.18
Zhang, Q. et al. Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture. Nat. Commun. 11, 1–11 (2020).
Holstege, H. et al. Exome sequencing identifies novel AD-associated genes. medRxiv 18, 24 (2020).
Psaty, B. M. et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circulation: Cardiovasc. Genet. 2, 73–80 (2009).
Naj, A. C. et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat. Genet. 43, 436–441 (2011).
pubmed: 21460841
pmcid: 3090745
doi: 10.1038/ng.801
Jun, G. et al. Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch. Neurol. 67, 1473–1484 (2010).
pubmed: 20697030
pmcid: 3048805
doi: 10.1001/archneurol.2010.201
Taliun, D. et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature 590, 290–299 (2021).
pubmed: 33568819
pmcid: 7875770
doi: 10.1038/s41586-021-03205-y
Das, S. et al. Next-generation genotype imputation service and methods. Nat. Genet. 48, 1284–1287 (2016).
pubmed: 27571263
pmcid: 5157836
doi: 10.1038/ng.3656
McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279–1283 (2016).
pubmed: 27548312
pmcid: 5388176
doi: 10.1038/ng.3643
Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).
pubmed: 17572673
doi: 10.1038/ng2088
Zhou, W. et al. Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat. Genet. 50, 1335–1341 (2018).
pubmed: 30104761
pmcid: 6119127
doi: 10.1038/s41588-018-0184-y
Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).
pubmed: 20616382
pmcid: 2922887
doi: 10.1093/bioinformatics/btq340
Aulchenko, Y. S., Ripke, S., Isaacs, A. & van Duijn, C. M. GenABEL: an R library for genome-wide association analysis. Bioinformatics 23, 1294–1296 (2007).
pubmed: 17384015
doi: 10.1093/bioinformatics/btm108
Bulik-Sullivan, B. et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291–295 (2015).
pubmed: 25642630
pmcid: 4495769
doi: 10.1038/ng.3211
de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11, e1004219 (2015).
pubmed: 25885710
pmcid: 4401657
doi: 10.1371/journal.pcbi.1004219
Yurko, R., Roeder, K., Devlin, B. & G’Sell, M. H‐MAGMA, inheriting a shaky statistical foundation, yields excess false positives. Ann. Hum. Genet. 85, 97–100 (2021).
pubmed: 33372276
doi: 10.1111/ahg.12412
De Leeuw, C. A., Neale, B. M., Heskes, T. & Posthuma, D. The statistical properties of gene-set analysis. Nat. Rev. Genet. 17, 353–364 (2016).
pubmed: 27070863
doi: 10.1038/nrg.2016.29
Storey, J. D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl Acad. Sci. U. S. A. 100, 9440–9445 (2003).
pubmed: 12883005
pmcid: 170937
doi: 10.1073/pnas.1530509100
Coelho, D. M., L. I. da Cruz Carvalho, Melo-de-Farias, A. R., Lambert, J.-C. & Costa, M. R. Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains. NPJ Aging Mech. Dis. 7, 2 (2021).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
pubmed: 29608179
pmcid: 6700744
doi: 10.1038/nbt.4096
Allen, M. et al. Human whole genome genotype and transcriptome data for Alzheimer’s and other neurodegenerative diseases. Sci. Data 3, 160089 (2016).
pubmed: 27727239
pmcid: 5058336
doi: 10.1038/sdata.2016.89
Mostafavi, S. et al. A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer’s disease. Nat. Neurosci. 21, 811–819 (2018).
pubmed: 29802388
pmcid: 6599633
doi: 10.1038/s41593-018-0154-9
Bennett, D. A. et al. Religious orders study and rush memory and aging project. J. Alzheimer’s Dis. 64, S161–S189 (2018).
doi: 10.3233/JAD-179939
Wang, M. et al. The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer’s disease. Sci. Data 5, 180185 (2018).
pubmed: 30204156
pmcid: 6132187
doi: 10.1038/sdata.2018.185
GTEx Consortium, The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318–1330 (2020).
doi: 10.1126/science.aaz1776
De, K. et al. Atlas of genetic effects in human microglia transcriptome across brain regions, aging and disease pathologies. Preprint at bioRxiv https://doi.org/10.1101/2020.10.27.356113 (2020).
Alasoo, K. et al. Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response. Nat. Genet. 50, 424–431 (2018).
pubmed: 29379200
pmcid: 6548559
doi: 10.1038/s41588-018-0046-7
Nédélec, Y. et al. Genetic ancestry and natural selection drive population differences in immune responses to pathogens. Cell 167, 657–669.e21 (2016).
pubmed: 27768889
doi: 10.1016/j.cell.2016.09.025
Chen, L. et al. Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell 167, 1398–1414.e24 (2016).
pubmed: 27863251
pmcid: 5119954
doi: 10.1016/j.cell.2016.10.026
Momozawa, Y. et al. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes. Nat. Commun. 9, 2427 (2018).
pubmed: 29930244
pmcid: 6013502
doi: 10.1038/s41467-018-04365-8
Fairfax, B. P. et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Sci. (80-.). 343, 1246949 (2014).
doi: 10.1126/science.1246949
Quach, H. et al. Genetic adaptation and neandertal admixture shaped the immune system of human populations. Cell 167, 643–656.e17 (2016).
pubmed: 27768888
pmcid: 5075285
doi: 10.1016/j.cell.2016.09.024
Kerimov, N. et al. eQTL catalogue: a compendium of uniformly processed human gene expression and splicing QTLs. Preprint at bioRxiv https://doi.org/10.1101/2020.01.29.924266 (2020).
Wingo, A. P. et al. Integrating human brain proteomes with genome-wide association data implicates new proteins in Alzheimer’s disease pathogenesis. Nat. Genet. 53, 143–146 (2021).
pubmed: 33510477
pmcid: 8130821
doi: 10.1038/s41588-020-00773-z
Ng, B. et al. An xQTL map integrates the genetic architecture of the human brain’s transcriptome and epigenome. Nat. Neurosci. 20, 1418–1426 (2017).
pubmed: 28869584
pmcid: 5785926
doi: 10.1038/nn.4632
Barbeira, A. N. et al. Exploiting the GTEx resources to decipher the mechanisms at GWAS loci. Genome Biol. 22, 49 (2021).
pubmed: 33499903
pmcid: 7836161
doi: 10.1186/s13059-020-02252-4
Edgar, R. D., Jones, M. J., Meaney, M. J., Turecki, G. & Kobor, M. S. BECon: a tool for interpreting DNA methylation findings from blood in the context of brain. Transl. Psychiatry 7, e1187 (2017).
pubmed: 28763057
pmcid: 5611738
doi: 10.1038/tp.2017.171
Freytag, V. et al. Genetic estimators of DNA methylation provide insights into the molecular basis of polygenic traits. Transl. Psychiatry 8, 31 (2018).
pubmed: 29382824
pmcid: 5802460
doi: 10.1038/s41398-017-0070-x
Barbeira, A. N. et al. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics. Nat. Commun. 9, 1825 (2018).
pubmed: 29739930
pmcid: 5940825
doi: 10.1038/s41467-018-03621-1
Chouraki, V. et al. Evaluation of a genetic risk score to improve risk prediction for Alzheimer’s disease. J. Alzheimers Dis. 53, 921–932 (2016).
pubmed: 27340842
pmcid: 5036102
doi: 10.3233/JAD-150749
Steyerberg, E. W. et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 21, 128–138 (2010).
pubmed: 20010215
pmcid: 3575184
doi: 10.1097/EDE.0b013e3181c30fb2
Harrell, F. E., Califf, R. M., Pryor, D. B., Lee, K. L. & Rosati, R. A. Evaluating the yield of medical tests. JAMA 247, 2543–2546 (1982).
pubmed: 7069920
doi: 10.1001/jama.1982.03320430047030
Gerds, T. A., Kattan, M. W., Schumacher, M. & Yu, C. Estimating a time-dependentconcordance index for survival prediction models with covariate dependent censoring. Stat. Med. 32, 2173–2184 (2013).
pubmed: 23172755
doi: 10.1002/sim.5681
Pencina, M. J., D’Agostino, R. B. & Steyerberg, E. W. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat. Med. 30, 11–21 (2011).
pubmed: 21204120
doi: 10.1002/sim.4085
Kattan, M. W. & Gerds, T. A. The index of prediction accuracy: an intuitive measure useful for evaluating risk prediction models. Diagnostic Progn. Res. 2, 7 (2018).
doi: 10.1186/s41512-018-0029-2
Viechtbauer, W. Conducting meta-analyses in R with the metafor. J. Stat. Softw. 36, 1–48 (2010).
doi: 10.18637/jss.v036.i03
Ozenne, B., Sørensen, A. L., Scheike, T., Torp-Pedersen, C. & Gerds, T. riskRegression: predicting the risk of an event using Cox regression models. R. J. 9, 440–460 (2017).
doi: 10.32614/RJ-2017-062