Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs
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Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2020-02-03
Date Acceptance
2019-12-02
Citation
PLoS Genetics, 2020, 16 (2), pp.1-23
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
23
Journal / Book Title
PLoS Genetics
Volume
16
Issue
2
Copyright Statement
© 2020 Ramdhani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008549
Subjects
Developmental Biology
0604 Genetics
Publication Status
Published
Date Publish Online
2020-02-03