Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3025522 99 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2021, The Author(s).
Έτος δημοσίευσης:
2021
Συγγραφείς:
de Rojas, I.
Moreno-Grau, S.
Tesi, N.
Grenier-Boley, B.
Andrade, V.
Jansen, I.E.
Pedersen, N.L.
Stringa, N.
Zettergren, A.
Hernández, I.
Montrreal, L.
Antúnez, C.
Antonell, A.
Tankard, R.M.
Bis, J.C.
Sims, R.
Bellenguez, C.
Quintela, I.
González-Perez, A.
Calero, M.
Franco-Macías, E.
Macías, J.
Blesa, R.
Cervera-Carles, L.
Menéndez-González, M.
Frank-García, A.
Royo, J.L.
Moreno, F.
Huerto Vilas, R.
Baquero, M.
Diez-Fairen, M.
Lage, C.
García-Madrona, S.
García-González, P.
Alarcón-Martín, E.
Valero, S.
Sotolongo-Grau, O.
Ullgren, A.
Naj, A.C.
Lemstra, A.W.
Benaque, A.
Pérez-Cordón, A.
Benussi, A.
Rábano, A.
Padovani, A.
Squassina, A.
de Mendonça, A.
Arias Pastor, A.
Kok, A.A.L.
Meggy, A.
Pastor, A.B.
Espinosa, A.
Corma-Gómez, A.
Martín Montes, A.
Sanabria, Á.
DeStefano, A.L.
Schneider, A.
Haapasalo, A.
Kinhult Ståhlbom, A.
Tybjærg-Hansen, A.
Hartmann, A.M.
Spottke, A.
Corbatón-Anchuelo, A.
Rongve, A.
Borroni, B.
Arosio, B.
Nacmias, B.
Nordestgaard, B.G.
Kunkle, B.W.
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Piñol-Ripoll, G.
Rábano, A.
Real de Asúa, D.
Rodrigo, S.
Rodríguez-Rodríguez, E.
Royo, J.L.
Ruiz, A.
Sanchez del Valle Díaz, R.
Sánchez-Juan, P.
Sastre, I.
Valero, S.
Vicente, M.P.
Vigo-Ortega, R.
Vivancos, L.
Macleod, C.
McCracken, C.
Brayne, C.
Bresner, C.
Grozeva, D.
Bellou, E.
Sommerville, E.W.
Matthews, F.
Leonenko, G.
Menzies, G.
Windle, G.
Harwood, J.
Phillips, J.
Bennett, K.
Luckuck, L.
Clare, L.
Woods, R.
Saad, S.
Burholt, V.
Jansen, I.E.
Rongve, A.
Kehoe, P.G.
Garcia-Ribas, G.
Sánchez-Juan, P.
Pastor, P.
Pérez-Tur, J.
Piñol-Ripoll, G.
Lopez de Munain, A.
García-Alberca, J.M.
Bullido, M.J.
Álvarez, V.
Lleó, A.
Real, L.M.
Scheltens, P.
Holstege, H.
Marquié, M.
Sáez, M.E.
Carracedo, Á.
Amouyel, P.
Schellenberg, G.D.
Williams, J.
Seshadri, S.
van Duijn, C.M.
Mather, K.A.
Sánchez-Valle, R.
Serrano-Ríos, M.
Orellana, A.
Tárraga, L.
Blennow, K.
Huisman, M.
Andreassen, O.A.
Posthuma, D.
Clarimón, J.
Boada, M.
van der Flier, W.M.
Ramirez, A.
Lambert, J.-C.
van der Lee, S.J.
Ruiz, A.
EADB contributors
The GR@ACE study group
DEGESCO consortium
IGAP (ADGC, CHARGE, EADI, GERAD)
PGC-ALZ consortia
Περιοδικό:
Nature Communications
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Τόμος:
12
Αριθμός / τεύχος:
1
Λέξεις-κλειδιά:
amyloid precursor protein; apolipoprotein E4; interleukin 34; amyloid precursor protein; apolipoprotein E; APP protein, human, detection method; genetic analysis; nervous system disorder; public health; risk assessment; risk factor; stratification, adult; Alzheimer disease; Article; case control study; CHRNE gene; female; gene; genetic association; genetic linkage; genetic risk; genetic risk score; genetic variation; genotype; heterozygote; homozygote; human; major clinical study; male; missense mutation; NDUFAF7 gene; onset age; PLCG2 gene; population structure; PRKD3 gene; SHARPIN gene; single nucleotide polymorphism; aged; Alzheimer disease; cohort analysis; follow up; genetic predisposition; genetics; genome-wide association study; information processing; metabolism; middle aged; multifactorial inheritance; pathology; procedures; risk assessment; risk factor; very elderly, Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Protein Precursor; Apolipoproteins E; 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; Risk Factors
Επίσημο URL (Εκδότης):
DOI:
10.1038/s41467-021-22491-8
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