Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs.
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,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1008549 |
| _version_ | 1819029827201531904 |
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| author | Satesh Ramdhani Elisa Navarro Evan Udine Anastasia G Efthymiou Brian M Schilder Madison Parks Alison Goate Towfique Raj |
| author_facet | Satesh Ramdhani Elisa Navarro Evan Udine Anastasia G Efthymiou Brian M Schilder Madison Parks Alison Goate Towfique Raj |
| author_sort | Satesh Ramdhani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T06:20:26Z |
| format | Article |
| id | doaj.art-eb27be45a81b461396b3b77f99c2d672 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-21T06:20:26Z |
| publishDate | 2020-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-eb27be45a81b461396b3b77f99c2d6722022-12-21T19:13:17ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042020-02-01162e100854910.1371/journal.pgen.1008549Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs.Satesh RamdhaniElisa NavarroEvan UdineAnastasia G EfthymiouBrian M SchilderMadison ParksAlison GoateTowfique RajRecent 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.https://doi.org/10.1371/journal.pgen.1008549 |
| spellingShingle | Satesh Ramdhani Elisa Navarro Evan Udine Anastasia G Efthymiou Brian M Schilder Madison Parks Alison Goate Towfique Raj Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. PLoS Genetics |
| title | Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. |
| title_full | Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. |
| title_fullStr | Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. |
| title_full_unstemmed | Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. |
| title_short | Tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease-specific trans-eQTLs. |
| title_sort | tensor decomposition of stimulated monocyte and macrophage gene expression profiles identifies neurodegenerative disease specific trans eqtls |
| url | https://doi.org/10.1371/journal.pgen.1008549 |
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