Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes
Until now, large-scale genome-wide association studies have identified 94 genes associated with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Expression quantitative trait locus (eQTL) analysis showed that six genetic variants around six of these 94 genes could drive bo...
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| Format: | Article |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00666/full |
| _version_ | 1818511600219324416 |
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| author | Jing-yi Sun Ya-jun Hou Yan Zhang Longcai Wang Lidong Liu Bao-liang Sun Hui Yuan |
| author_facet | Jing-yi Sun Ya-jun Hou Yan Zhang Longcai Wang Lidong Liu Bao-liang Sun Hui Yuan |
| author_sort | Jing-yi Sun |
| collection | DOAJ |
| description | Until now, large-scale genome-wide association studies have identified 94 genes associated with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Expression quantitative trait locus (eQTL) analysis showed that six genetic variants around six of these 94 genes could drive both disease susceptibility and altered expression of six nearby genes including CD33 (rs3865444), PILRB (rs1476679), NUP160 (rs10838725), LRRK2 (rs76904798), RGS1 (rs1323292), and METTL21B (rs701006). However, two of these six genetic variants rs1476679 and rs76904798 variants could regulate the expression of PILRB and LRRK2 only in the human monocyte-derived microglia-like (MDMi) cells, but not in human peripheral blood monocytes. Here, we aim to verify these findings using another two eQTL datasets in human peripheral blood immune cell CD14+ monocytes. The results that showed that rs1476679 and rs76904798 variants or their proxy variants could significantly regulate the expression of PILRB and LRRK2 in immune cell CD14+ monocytes and human peripheral blood. We believe that these findings provide important supplementary information about the regulatory mechanisms by which both variants influence PILRB and LRRK2 gene expression and neurodegenerative disease risk. |
| first_indexed | 2024-12-10T23:35:18Z |
| format | Article |
| id | doaj.art-24f5250d9edd413e84593728cdff8736 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T23:35:18Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-24f5250d9edd413e84593728cdff87362022-12-22T01:29:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-12-01910.3389/fgene.2018.00666429366Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ MonocytesJing-yi Sun0Ya-jun Hou1Yan Zhang2Longcai Wang3Lidong Liu4Bao-liang Sun5Hui Yuan6Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South KoreaKey Laboratory of Cerebral Microcirculation, Department of Neurology, Affiliated Hospital of Taishan Medical University, Universities of Shandong, Taian, ChinaDepartment of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Weifang Medical University, Weifang, ChinaBrain Research Centre, University of British Columbia, Vancouver, BC, CanadaKey Laboratory of Cerebral Microcirculation, Department of Neurology, Affiliated Hospital of Taishan Medical University, Universities of Shandong, Taian, ChinaKey Laboratory of Cerebral Microcirculation, Department of Neurology, Affiliated Hospital of Taishan Medical University, Universities of Shandong, Taian, ChinaUntil now, large-scale genome-wide association studies have identified 94 genes associated with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Expression quantitative trait locus (eQTL) analysis showed that six genetic variants around six of these 94 genes could drive both disease susceptibility and altered expression of six nearby genes including CD33 (rs3865444), PILRB (rs1476679), NUP160 (rs10838725), LRRK2 (rs76904798), RGS1 (rs1323292), and METTL21B (rs701006). However, two of these six genetic variants rs1476679 and rs76904798 variants could regulate the expression of PILRB and LRRK2 only in the human monocyte-derived microglia-like (MDMi) cells, but not in human peripheral blood monocytes. Here, we aim to verify these findings using another two eQTL datasets in human peripheral blood immune cell CD14+ monocytes. The results that showed that rs1476679 and rs76904798 variants or their proxy variants could significantly regulate the expression of PILRB and LRRK2 in immune cell CD14+ monocytes and human peripheral blood. We believe that these findings provide important supplementary information about the regulatory mechanisms by which both variants influence PILRB and LRRK2 gene expression and neurodegenerative disease risk.https://www.frontiersin.org/article/10.3389/fgene.2018.00666/fullgenome-wide association studyneurodegenerative diseaseeQTLsCD14+ monocytesAlzheimer's disease |
| spellingShingle | Jing-yi Sun Ya-jun Hou Yan Zhang Longcai Wang Lidong Liu Bao-liang Sun Hui Yuan Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes Frontiers in Genetics genome-wide association study neurodegenerative disease eQTLs CD14+ monocytes Alzheimer's disease |
| title | Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes |
| title_full | Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes |
| title_fullStr | Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes |
| title_full_unstemmed | Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes |
| title_short | Genetic Variants Associated With Neurodegenerative Diseases Regulate Gene Expression in Immune Cell CD14+ Monocytes |
| title_sort | genetic variants associated with neurodegenerative diseases regulate gene expression in immune cell cd14 monocytes |
| topic | genome-wide association study neurodegenerative disease eQTLs CD14+ monocytes Alzheimer's disease |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00666/full |
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