Title | Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernández I et al. |
Corporate Authors | EADB contributors, GR@ACE study group, DEGESCO consortium, IGAP(ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia |
Journal | Nat Commun |
Volume | 12 |
Issue | 1 |
Pagination | 3417 |
Date Published | 2021 06 07 |
ISSN | 2041-1723 |
Keywords | 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 |
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. |
DOI | 10.1038/s41467-021-22491-8 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/34099642?dopt=Abstract |
page_expo | External |
Alternate Journal | Nat Commun |
PubMed ID | 34099642 |
PubMed Central ID | PMC8184987 |
Grant List | U24 AG021886 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States U01 AG058589 / AG / NIA NIH HHS / United States 082604/2/07/Z / WT_ / Wellcome Trust / United Kingdom / WT_ / Wellcome Trust / United Kingdom MR/L010305/1 / MRC_ / Medical Research Council / United Kingdom U01 AG049505 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States 503480 / MRC_ / Medical Research Council / United Kingdom |
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