Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes
Abstract Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-84817-y |
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| author | Riley H. Tough Paul J. McLaren The International Collaboration for the Genomics of HIV |
| author_facet | Riley H. Tough Paul J. McLaren The International Collaboration for the Genomics of HIV |
| author_sort | Riley H. Tough |
| collection | DOAJ |
| description | Abstract Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, CHD1L, enhanced HIV replication in vitro in myeloid cells. However, it remains unclear if HIV spVL associated variants are associated with CHD1L gene expression changes. Here we apply a heuristic fine-mapping approach to prioritize combinations of variants that explain the majority of set-point viral load variance and identify variants likely driving the association. We assess the combined impact of these variants on CHD1L regulation using publicly available sequencing studies, and test the relationship between CHD1L expression and set-point viral load using imputed CHD1L expression from monocytes. Taken together, this work characterizes genetically regulated CHD1L expression and further expands our knowledge of CHD1L-mediated HIV restriction in monocytes. |
| format | Article |
| id | doaj-art-dacd6f5df31941ed93323a380406c6d0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dacd6f5df31941ed93323a380406c6d02025-01-19T12:20:27ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-024-84817-yFunctionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytesRiley H. Tough0Paul J. McLaren1The International Collaboration for the Genomics of HIVSexually Transmitted and Bloodborne Infections Surveillance and Molecular Epidemiology, Sexually Transmitted and Bloodborne Infections Division at the JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratories, Public Health Agency of CanadaSexually Transmitted and Bloodborne Infections Surveillance and Molecular Epidemiology, Sexually Transmitted and Bloodborne Infections Division at the JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratories, Public Health Agency of CanadaAbstract Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, CHD1L, enhanced HIV replication in vitro in myeloid cells. However, it remains unclear if HIV spVL associated variants are associated with CHD1L gene expression changes. Here we apply a heuristic fine-mapping approach to prioritize combinations of variants that explain the majority of set-point viral load variance and identify variants likely driving the association. We assess the combined impact of these variants on CHD1L regulation using publicly available sequencing studies, and test the relationship between CHD1L expression and set-point viral load using imputed CHD1L expression from monocytes. Taken together, this work characterizes genetically regulated CHD1L expression and further expands our knowledge of CHD1L-mediated HIV restriction in monocytes.https://doi.org/10.1038/s41598-024-84817-y |
| spellingShingle | Riley H. Tough Paul J. McLaren The International Collaboration for the Genomics of HIV Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes Scientific Reports |
| title | Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes |
| title_full | Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes |
| title_fullStr | Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes |
| title_full_unstemmed | Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes |
| title_short | Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes |
| title_sort | functionally informed fine mapping identifies genetic variants linking increased chd1l expression and hiv restriction in monocytes |
| url | https://doi.org/10.1038/s41598-024-84817-y |
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