Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines.
Alzheimer Disease
/ genetics
Amyloid Precursor Protein Secretases
/ genetics
Aspartic Acid Endopeptidases
/ genetics
Cell Line
Gene Expression
Genome-Wide Association Study
Humans
LDL-Receptor Related Proteins
/ genetics
Lymphocytes
/ metabolism
Membrane Transport Proteins
/ genetics
MicroRNAs
/ genetics
Negative Results
Polymorphism, Single Nucleotide
Quantitative Trait Loci
/ genetics
Risk
Alzheimer's disease
GWAS
Gene expression
Genetic association
eQTLs
miRNA
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
11
07
2018
revised:
23
07
2019
accepted:
14
08
2019
pubmed:
7
11
2019
medline:
8
9
2020
entrez:
6
11
2019
Statut:
ppublish
Résumé
The role of microRNAs (miRNAs) in the pathogenesis of Alzheimer's disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from 3 AD genome-wide association studies (GWASs). Association with miRNA expression was tested by expression quantitative trait locus analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines. Although, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type, we highlight 2 notable outliers, that is, miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite 2 exceptions, our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA expression quantitative trait loci.
Identifiants
pubmed: 31685236
pii: S0197-4580(19)30291-X
doi: 10.1016/j.neurobiolaging.2019.08.013
pii:
doi:
Substances chimiques
LDL-Receptor Related Proteins
0
Membrane Transport Proteins
0
MicroRNAs
0
SORL1 protein, human
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Aspartic Acid Endopeptidases
EC 3.4.23.-
BACE1 protein, human
EC 3.4.23.46
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
202.e1-202.e3Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.