Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs.
Alzheimer Disease
/ genetics
Cell Line
Chromosome Mapping
Datasets as Topic
Gene Expression Profiling
Gene Regulatory Networks
/ immunology
Genetic Predisposition to Disease
Genetic Variation
/ immunology
Genome-Wide Association Study
Humans
Immunity, Innate
/ genetics
Interferon-gamma
/ immunology
Lipopolysaccharides
/ immunology
Macrophages
/ immunology
Models, Genetic
Monocytes
/ immunology
Oligonucleotide Array Sequence Analysis
Parkinson Disease
/ genetics
Quantitative Trait Loci
/ immunology
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
11
06
2019
accepted:
02
12
2019
revised:
13
02
2020
pubmed:
6
2
2020
medline:
12
5
2020
entrez:
4
2
2020
Statut:
epublish
Résumé
Recent human genetic studies suggest that cells of the innate immune system have a primary role in the pathogenesis of neurodegenerative diseases. However, the results from these studies often do not elucidate how the genetic variants affect the biology of these cells to modulate disease risk. Here, we applied a tensor decomposition method to uncover disease associated gene networks linked to distal genetic variation in stimulated human monocyte and macrophage gene expression profiles. We report robust evidence that some disease associated genetic variants affect the expression of multiple genes in trans. These include a Parkinson's disease locus influencing the expression of genes mediated by a protease that controls lysosomal function, and Alzheimer's disease loci influencing the expression of genes involved in type 1 interferon signaling, myeloid phagocytosis, and complement cascade pathways. Overall, we uncover gene networks in induced innate immune cells linked to disease associated genetic variants, which may help elucidate the underlying biology of disease.
Identifiants
pubmed: 32012164
doi: 10.1371/journal.pgen.1008549
pii: PGENETICS-D-19-00935
pmc: PMC7018232
doi:
Substances chimiques
Lipopolysaccharides
0
Interferon-gamma
82115-62-6
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
e1008549Subventions
Organisme : NIA NIH HHS
ID : R01 AG054005
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIH HHS
ID : S10 OD026880
Pays : United States
Déclaration de conflit d'intérêts
AG served on the scientific advisory board for Denali Therapeutics from 2015-2018 and has served as a consultant to AbbVie, Biogen, Eisai, Illumina, and GSK. Other authors declare no competing financial interests.
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