Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data
Abstract Background The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-021-00306-7 |
| _version_ | 1818001756897935360 |
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| author | Jianchang Hu Cai Li Shiying Wang Ting Li Heping Zhang |
| author_facet | Jianchang Hu Cai Li Shiying Wang Ting Li Heping Zhang |
| author_sort | Jianchang Hu |
| collection | DOAJ |
| description | Abstract Background The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors. Methods In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations. Results We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2. Conclusions Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options. |
| first_indexed | 2024-04-14T03:38:26Z |
| format | Article |
| id | doaj.art-280e857bcf3f4168b7c5ea2d16594fa4 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-14T03:38:26Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-280e857bcf3f4168b7c5ea2d16594fa42022-12-22T02:14:39ZengBMCHuman Genomics1479-73642021-02-0115111010.1186/s40246-021-00306-7Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank dataJianchang Hu0Cai Li1Shiying Wang2Ting Li3Heping Zhang4Department of Biostatistics, Yale UniversityDepartment of Biostatistics, Yale UniversityDepartment of Biostatistics, Yale UniversityDepartment of Biostatistics, Yale UniversityDepartment of Biostatistics, Yale UniversityAbstract Background The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors. Methods In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations. Results We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2. Conclusions Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.https://doi.org/10.1186/s40246-021-00306-7COVID-19GWASHost genetic factorsMortalitySARS-CoV-2UK Biobank |
| spellingShingle | Jianchang Hu Cai Li Shiying Wang Ting Li Heping Zhang Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data Human Genomics COVID-19 GWAS Host genetic factors Mortality SARS-CoV-2 UK Biobank |
| title | Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data |
| title_full | Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data |
| title_fullStr | Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data |
| title_full_unstemmed | Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data |
| title_short | Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data |
| title_sort | genetic variants are identified to increase risk of covid 19 related mortality from uk biobank data |
| topic | COVID-19 GWAS Host genetic factors Mortality SARS-CoV-2 UK Biobank |
| url | https://doi.org/10.1186/s40246-021-00306-7 |
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