Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs
Autoři:
Satesh Ramdhani aff001; Elisa Navarro aff001; Evan Udine aff001; Anastasia G. Efthymiou aff001; Brian M. Schilder aff001; Madison Parks aff001; Alison Goate aff001; Towfique Raj aff001
Působiště autorů:
Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
aff001; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
aff002; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
aff003
Vyšlo v časopise:
Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. PLoS Genet 16(2): e32767. doi:10.1371/journal.pgen.1008549
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008549
Souhrn
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.
Klíčová slova:
Alzheimer's disease – Gene expression – Genetic loci – Genome-wide association studies – Interferons – Macrophages – Monocytes – Parkinson disease
Zdroje
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