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Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs.

TitleTensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs.
Publication TypeJournal Article
Year of Publication2020
AuthorsRamdhani S, Navarro E, Udine E, Efthymiou AG, Schilder BM, Parks M, Goate A, Raj T
JournalPLoS Genet
Volume16
Issue2
Paginatione1008549
Date Published2020 02
ISSN1553-7404
KeywordsAlzheimer Disease, Cell Line, Chromosome Mapping, Datasets as Topic, Gene Expression Profiling, Gene Regulatory Networks, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Immunity, Innate, Interferon-gamma, Lipopolysaccharides, Macrophages, Models, Genetic, Monocytes, Oligonucleotide Array Sequence Analysis, Parkinson Disease, Quantitative Trait Loci
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.

DOI10.1371/journal.pgen.1008549
Pubmed Linkhttps://www.ncbi.nlm.nih.gov/pubmed/32012164?dopt=Abstract
page_expoExternal
Alternate JournalPLoS Genet
PubMed ID32012164
PubMed Central IDPMC7018232
Grant ListR01 AG054005 / AG / NIA NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
S10 OD026880 / OD / NIH HHS / United States

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