Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
Age of Onset
Aged
Aged, 80 and over
Alzheimer Disease
/ epidemiology
Amyloid beta-Protein Precursor
/ genetics
Apolipoproteins E
/ genetics
Case-Control Studies
Cohort Studies
Datasets as Topic
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Heterozygote
Humans
Male
Middle Aged
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Assessment
/ methods
Risk Factors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
17
07
2020
accepted:
17
03
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
Identifiants
pubmed: 34099642
doi: 10.1038/s41467-021-22491-8
pii: 10.1038/s41467-021-22491-8
pmc: PMC8184987
doi:
Substances chimiques
APP protein, human
0
Amyloid beta-Protein Precursor
0
Apolipoproteins E
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
3417Subventions
Organisme : Medical Research Council
ID : MC_PC_17112
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS017950
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067501
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : Medical Research Council
ID : MR/M009076/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0601022
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : N01AG12100
Pays : United States
Organisme : Wellcome Trust
ID : 082604/2/07/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9901400
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG049505
Pays : United States
Organisme : Medical Research Council
ID : G0902227
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG054076
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00024/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MR/K013041/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : 503480
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : Medical Research Council
ID : G1100540
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG058589
Pays : United States
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300429
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900652
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG066546
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052409
Pays : United States
Organisme : Medical Research Council
ID : G0400074
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501517/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0502157
Pays : United Kingdom
Investigateurs
A David Smith
(AD)
Aldo Saenz
(A)
Alessandra Bizzarro
(A)
Alessandra Lauria
(A)
Alessandro Vacca
(A)
Alina Solomon
(A)
Anna Anastasiou
(A)
Anna Richardson
(A)
Anne Boland
(A)
Anne Koivisto
(A)
Antonio Daniele
(A)
Antonio Greco
(A)
Arnaoutoglou Marianthi
(A)
Bernadette McGuinness
(B)
Bertrand Fin
(B)
Camilla Ferrari
(C)
Carlo Custodero
(C)
Carlo Ferrarese
(C)
Carlos Ingino
(C)
Carlos Mangone
(C)
Carlos Reyes Toso
(C)
Carmen Martínez
(C)
Carolina Cuesta
(C)
Carolina Muchnik
(C)
Catharine Joachim
(C)
Cecilia Ortiz
(C)
Céline Besse
(C)
Charlotte Johansson
(C)
Chiara Paola Zoia
(CP)
Christoph Laske
(C)
Costas Anastasiou
(C)
Dana Lis Palacio
(DL)
Daniel G Politis
(DG)
Daniel Janowitz
(D)
David Craig
(D)
David M Mann
(DM)
David Neary
(D)
Deckert Jürgen
(D)
Delphine Daian
(D)
Diyana Belezhanska
(D)
Eduardo Kohler
(E)
Eduardo M Castaño
(EM)
Effrosyni Koutsouraki
(E)
Elena Chipi
(E)
Ellen De Roeck
(E)
Emanuele Costantini
(E)
Emma R L C Vardy
(ERLC)
Fabrizio Piras
(F)
Fausto Roveta
(F)
Federica Piras
(F)
Federico Ariel Prestia
(FA)
Francesca Assogna
(F)
Francesca Salani
(F)
Gessica Sala
(G)
Giordano Lacidogna
(G)
Gisela Novack
(G)
Gordon Wilcock
(G)
Håkan Thonberg
(H)
Heike Kölsch
(H)
Heike Weber
(H)
Henning Boecker
(H)
Ignacio Etchepareborda
(I)
Irene Piaceri
(I)
Jaakko Tuomilehto
(J)
Jaana Lindström
(J)
Jan Laczo
(J)
Janet Johnston
(J)
Jean-François Deleuze
(JF)
Jenny Harris
(J)
Jonathan M Schott
(JM)
Josef Priller
(J)
Juan Ignacio Bacha
(JI)
Julie Snowden
(J)
Julieta Lisso
(J)
Kalina Yonkova Mihova
(KY)
Latchezar Traykov
(L)
Laura Morelli
(L)
Luis Ignacio Brusco
(LI)
Malik Rainer
(M)
Mari Takalo
(M)
Maria Bjerke
(M)
Maria Del Zompo
(M)
Maria Serpente
(M)
Mariana Sanchez Abalos
(M)
Mario Rios
(M)
Markku Peltonen
(M)
Martin J Herrman
(MJ)
Mary H Kosmidis
(MH)
Matias Kohler
(M)
Matias Rojo
(M)
Matthew Jones
(M)
Michela Orsini
(M)
Nancy Medel
(N)
Natividad Olivar
(N)
Nick C Fox
(NC)
Nicola Salvadori
(N)
Nigel M Hooper
(NM)
Pablo Galeano
(P)
Patricia Solis
(P)
Patrizia Bastiani
(P)
Peter Passmore
(P)
Reinhard Heun
(R)
Riitta Antikainen
(R)
Robert Olaso
(R)
Robert Perneczky
(R)
Sandra Germani
(S)
Sara López-García
(S)
Seth Love
(S)
Shima Mehrabian
(S)
Silvia Bagnoli
(S)
Silvia Kochen
(S)
Simona Andreoni
(S)
Stefan Teipel
(S)
Stephen Todd
(S)
Stuart Pickering-Brown
(S)
Teemu Natunen
(T)
Thomas Tegos
(T)
Tiina Laatikainen
(T)
Timo Strandberg
(T)
Tuomo M Polvikoski
(TM)
Vaclav Matoska
(V)
Valentina Ciullo
(V)
Valeria Cores
(V)
Vincenzo Solfrizzi
(V)
Viviana Lisetti
(V)
Zulma Sevillano
(Z)
C Abdelnour
(C)
N Aguilera
(N)
E Alarcon
(E)
M Alegret
(M)
A Benaque
(A)
M Boada
(M)
M Buendia
(M)
P Cañabate
(P)
A Carracedo
(A)
A Corbatón-Anchuelo
(A)
I de Rojas
(I)
S Diego
(S)
A Espinosa
(A)
A Gailhajenet
(A)
P García-González
(P)
S Gil
(S)
M Guitart
(M)
A González-Pérez
(A)
I Hernández
(I)
M Ibarria
(M)
A Lafuente
(A)
J Macias
(J)
O Maroñas
(O)
E Martín
(E)
M T Martínez
(MT)
M Marquié
(M)
A Mauleón
(A)
L Montrreal
(L)
S Moreno-Grau
(S)
M Moreno
(M)
A Orellana
(A)
G Ortega
(G)
A Pancho
(A)
E Pelejá
(E)
A Pérez-Cordon
(A)
J A Pineda
(JA)
S Preckler
(S)
I Quintela
(I)
L M Real
(LM)
M Rosende-Roca
(M)
A Ruiz
(A)
M E Sáez
(ME)
A Sanabria
(A)
M Serrano-Rios
(M)
O Sotolongo-Grau
(O)
L Tárraga
(L)
S Valero
(S)
L Vargas
(L)
A D Adarmes-Gómez
(AD)
E Alarcón-Martín
(E)
M D Alonso
(MD)
I Álvarez
(I)
V Álvarez
(V)
G Amer-Ferrer
(G)
M Antequera
(M)
C Antúnez
(C)
M Baquero
(M)
M Bernal
(M)
R Blesa
(R)
M Boada
(M)
D Buiza-Rueda
(D)
M J Bullido
(MJ)
J A Burguera
(JA)
M Calero
(M)
F Carrillo
(F)
M Carrión-Claro
(M)
M J Casajeros
(MJ)
J Clarimón
(J)
J M Cruz-Gamero
(JM)
M M de Pancorbo
(MM)
I de Rojas
(I)
T Del Ser
(T)
M Diez-Fairen
(M)
R Escuela
(R)
L Garrote-Espina
(L)
J Fortea
(J)
E Franco-Macías
(E)
A Frank-García
(A)
J M García-Alberca
(JM)
S Garcia Madrona
(S)
G Garcia-Ribas
(G)
P Gómez-Garre
(P)
I Hernández
(I)
S Hevilla
(S)
S Jesús
(S)
M A Labrador Espinosa
(MA)
C Lage
(C)
A Legaz
(A)
A Lleó
(A)
A Lopez de Munain
(A)
S López-García
(S)
D Macias-García
(D)
S Manzanares
(S)
M Marín
(M)
J Marín-Muñoz
(J)
T Marín
(T)
M Marquié
(M)
A Martín Montes
(A)
B Martínez
(B)
C Martínez
(C)
V Martínez
(V)
P Martínez-Lage Álvarez
(P)
M Medina
(M)
M Mendioroz Iriarte
(M)
M Menéndez-González
(M)
P Mir
(P)
J L Molinuevo
(JL)
P Pastor
(P)
J Pérez Tur
(J)
T Periñán-Tocino
(T)
R Pineda-Sanchez
(R)
G Piñol-Ripoll
(G)
A Rábano
(A)
D Real de Asúa
(D)
S Rodrigo
(S)
E Rodríguez-Rodríguez
(E)
J L Royo
(JL)
A Ruiz
(A)
R Sanchez Del Valle Díaz
(R)
P Sánchez-Juan
(P)
I Sastre
(I)
S Valero
(S)
M P Vicente
(MP)
R Vigo-Ortega
(R)
L Vivancos
(L)
C Macleod
(C)
C McCracken
(C)
Carol Brayne
(C)
Catherine Bresner
(C)
Detelina Grozeva
(D)
Eftychia Bellou
(E)
Ewen W Sommerville
(EW)
F Matthews
(F)
Ganna Leonenko
(G)
Georgina Menzies
(G)
Gill Windle
(G)
Janet Harwood
(J)
Judith Phillips
(J)
K Bennett
(K)
Lauren Luckuck
(L)
Linda Clare
(L)
Robert Woods
(R)
Salha Saad
(S)
Vanessa Burholt
(V)
Iris E Jansen
(IE)
Arvid Rongve
(A)
Commentaires et corrections
Type : ErratumIn
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