Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene
Summary: The host genetic factors conferring protection against HIV type 1 (HIV-1) acquisition remain elusive, and in particular the contributions of common genetic variants. Here, we performed the largest genome-wide association meta-analysis of HIV-1 acquisition, which included 7,303 HIV-1-positiv...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222011269 |
| _version_ | 1811214793615343616 |
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| author | Rodrigo R.R. Duarte Oliver Pain Robert L. Furler Douglas F. Nixon Timothy R. Powell |
| author_facet | Rodrigo R.R. Duarte Oliver Pain Robert L. Furler Douglas F. Nixon Timothy R. Powell |
| author_sort | Rodrigo R.R. Duarte |
| collection | DOAJ |
| description | Summary: The host genetic factors conferring protection against HIV type 1 (HIV-1) acquisition remain elusive, and in particular the contributions of common genetic variants. Here, we performed the largest genome-wide association meta-analysis of HIV-1 acquisition, which included 7,303 HIV-1-positive individuals and 587,343 population controls. We identified 25 independent genetic loci with suggestive association, of which one was genome-wide significant within the major histocompatibility complex (MHC) locus. After exclusion of the MHC signal, linkage disequilibrium score regression analyses revealed a SNP heritability of 21% and genetic correlations with behavioral factors. A transcriptome-wide association study identified 15 susceptibility genes, including HERC1, UEVLD, and HIST1H4K. Convergent evidence from conditional analyses and fine-mapping identified HERC1 downregulation in immune cells as a robust mechanism associated with HIV-1 acquisition. Functional studies on HERC1 and other identified candidates, as well as larger genetic studies, have the potential to further our understanding of the host mechanisms associated with protection against HIV-1. |
| first_indexed | 2024-04-12T06:11:33Z |
| format | Article |
| id | doaj.art-54145ed61d944536a089b89e3c45b8ad |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T06:11:33Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-54145ed61d944536a089b89e3c45b8ad2022-12-22T03:44:42ZengElsevieriScience2589-00422022-09-01259104854Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility geneRodrigo R.R. Duarte0Oliver Pain1Robert L. Furler2Douglas F. Nixon3Timothy R. Powell4Department of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, London, SE5 8AF, UK; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, 10021, USA; Corresponding authorDepartment of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, London, SE5 8AF, UKDivision of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, 10021, USADivision of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, 10021, USADepartment of Social, Genetic & Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, London, SE5 8AF, UK; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, 10021, USASummary: The host genetic factors conferring protection against HIV type 1 (HIV-1) acquisition remain elusive, and in particular the contributions of common genetic variants. Here, we performed the largest genome-wide association meta-analysis of HIV-1 acquisition, which included 7,303 HIV-1-positive individuals and 587,343 population controls. We identified 25 independent genetic loci with suggestive association, of which one was genome-wide significant within the major histocompatibility complex (MHC) locus. After exclusion of the MHC signal, linkage disequilibrium score regression analyses revealed a SNP heritability of 21% and genetic correlations with behavioral factors. A transcriptome-wide association study identified 15 susceptibility genes, including HERC1, UEVLD, and HIST1H4K. Convergent evidence from conditional analyses and fine-mapping identified HERC1 downregulation in immune cells as a robust mechanism associated with HIV-1 acquisition. Functional studies on HERC1 and other identified candidates, as well as larger genetic studies, have the potential to further our understanding of the host mechanisms associated with protection against HIV-1.http://www.sciencedirect.com/science/article/pii/S2589004222011269GeneticsImmunityBioinformatics |
| spellingShingle | Rodrigo R.R. Duarte Oliver Pain Robert L. Furler Douglas F. Nixon Timothy R. Powell Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene iScience Genetics Immunity Bioinformatics |
| title | Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene |
| title_full | Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene |
| title_fullStr | Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene |
| title_full_unstemmed | Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene |
| title_short | Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene |
| title_sort | transcriptome wide association study of hiv 1 acquisition identifies herc1 as a susceptibility gene |
| topic | Genetics Immunity Bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222011269 |
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