Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
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Date
2021-06-07
Authors
de-Rojas, Itziar
Moreno-Grau, Sonia
Tesi, Niccolo
Grenier-Boley, Benjamin
Andrade, Victor
Jansen, Iris E
Pedersen, Nancy L
Stringa, Najada
Zettergren, Anna
Hernández, Isabel
Advisors
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Publisher
Nature Publishing Group
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Abstract
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.
Description
MeSH Terms
Aged
Aged, 80 and over
Amyloid beta-Protein Precursor
Case-Control Studies
Cohort Studies
Female
Follow-Up Studies
Heterozygote
Humans
Middle Aged
Multifactorial Inheritance
Risk Assessment
Aged, 80 and over
Amyloid beta-Protein Precursor
Case-Control Studies
Cohort Studies
Female
Follow-Up Studies
Heterozygote
Humans
Middle Aged
Multifactorial Inheritance
Risk Assessment
DeCS Terms
Enfermedad de Alzheimer
Puntuación de riesgo genético
Apolipoproteínas E
Comprensión
Amiloide
Estudios de asociación genética
Apoderado
Conductores
Puntuación de riesgo genético
Apolipoproteínas E
Comprensión
Amiloide
Estudios de asociación genética
Apoderado
Conductores
CIE Terms
Keywords
Age of Onset, Alzheimer Disease, Apolipoproteins E, Datasets as Topic, Genetic Predisposition to Disease, Genome-Wide Association Study, Male, Polymorphism, Single Nucleotide, Risk Factors
Citation
de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, et al. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nat Commun. 2021 Jun 7;12(1):3417.