Cell-type-specific expression quantitative trait loci associated with Alzheimer disease in blood and brain tissue.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
27 04 2021
27 04 2021
Historique:
received:
06
11
2020
accepted:
08
04
2021
revised:
24
03
2021
entrez:
28
4
2021
pubmed:
29
4
2021
medline:
29
6
2021
Statut:
epublish
Résumé
Because regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1 Mb of genes was evaluated using linear regression models for unrelated subjects and linear-mixed models for related subjects. Cell-type-specific eQTL (ct-eQTL) models included an interaction term for the expression of "proxy" genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell types is supported by the observation that a large portion of GWS ct-eQTLs map within 1 Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type-specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type-specific analysis.
Identifiants
pubmed: 33907181
doi: 10.1038/s41398-021-01373-z
pii: 10.1038/s41398-021-01373-z
pmc: PMC8079392
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
250Subventions
Organisme : NIA NIH HHS
ID : R01 AG064932
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056318
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG072577
Pays : United States
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