TY - JOUR
T1 - Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
AU - EADB contributors
AU - The GR@ACE study group
AU - DEGESCO consortium
AU - IGAP (ADGC, CHARGE, EADI, GERAD)
AU - PGC-ALZ consortia
AU - de Rojas, Itziar
AU - Moreno-Grau, Sonia
AU - Tesi, Niccolo
AU - Grenier-Boley, Benjamin
AU - Andrade, Victor
AU - Jansen, Iris E.
AU - Pedersen, Nancy L.
AU - Stringa, Najada
AU - Zettergren, Anna
AU - Hernández, Isabel
AU - Montrreal, Laura
AU - Antúnez, Carmen
AU - Antonell, Anna
AU - Tankard, Rick M.
AU - Bis, Joshua C.
AU - Sims, Rebecca
AU - Bellenguez, Céline
AU - Quintela, Inés
AU - González-Perez, Antonio
AU - Calero, Miguel
AU - Franco-Macías, Emilio
AU - Macías, Juan
AU - Blesa, Rafael
AU - Cervera-Carles, Laura
AU - Menéndez-González, Manuel
AU - Frank-García, Ana
AU - Royo, Jose Luís
AU - Moreno, Fermin
AU - Huerto Vilas, Raquel
AU - Baquero, Miquel
AU - Diez-Fairen, Mónica
AU - Lage, Carmen
AU - García-Madrona, Sebastián
AU - García-González, Pablo
AU - Alarcón-Martín, Emilio
AU - Valero, Sergi
AU - Sotolongo-Grau, Oscar
AU - Ullgren, Abbe
AU - Naj, Adam C.
AU - Lemstra, Afina W.
AU - Benaque, Alba
AU - Pérez-Cordón, Alba
AU - Benussi, Alberto
AU - Rábano, Alberto
AU - Padovani, Alessandro
AU - Squassina, Alessio
AU - Satizabal, Claudia L.
AU - Jian, Xueqiu
AU - Seshadri, Sudha
AU - Ruiz, Agustín
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-22491-8
DO - 10.1038/s41467-021-22491-8
M3 - Article
C2 - 34099642
AN - SCOPUS:85107895788
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3417
ER -