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ELF5 is a potential...
ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19
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Pietzner, M (author)
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Chua, RL (author)
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Wheeler, E (author)
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Jechow, K (author)
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Willett, JDS (author)
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Radbruch, H (author)
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Trump, S (author)
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Heidecker, B (author)
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- Zeberg, H (author)
- Karolinska Institutet
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Heppner, FL (author)
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Eils, R (author)
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Mall, MA (author)
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Richards, JB (author)
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Sander, LE (author)
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Lehmann, I (author)
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Lukassen, S (author)
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Wareham, NJ (author)
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Conrad, C (author)
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Langenberg, C (author)
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(creator_code:org_t)
- 2022-08-15
- 2022
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4484-
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Abstract
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- Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis of COVID-19 infection remain poorly understood. Here, we prioritise eight robust (e.g., ELF5) or suggestive but unreported (e.g., RAB2A) candidate protein mediators of COVID-19 outcomes by integrating results from the COVID-19 Host Genetics Initiative with population-based plasma proteomics using statistical colocalisation. The transcription factor ELF5 (ELF5) shows robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.88; 95%-CI: 2.47–9.63; p-value < 5.0 × 10−6) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5. We show that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells, using single-cell RNA sequencing and immunohistochemistry. These cells are also likely targets of SARS-CoV-2 by colocalisation with key host factors, including ACE2 and TMPRSS2. In summary, large-scale human genetic studies together with gene expression at single-cell resolution highlight ELF5 as a risk gene for severe COVID-19, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2.
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- By the author/editor
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Pietzner, M
-
Chua, RL
-
Wheeler, E
-
Jechow, K
-
Willett, JDS
-
Radbruch, H
-
show more...
-
Trump, S
-
Heidecker, B
-
Zeberg, H
-
Heppner, FL
-
Eils, R
-
Mall, MA
-
Richards, JB
-
Sander, LE
-
Lehmann, I
-
Lukassen, S
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Wareham, NJ
-
Conrad, C
-
Langenberg, C
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show less...
- Articles in the publication
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Nature communica ...
- By the university
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Karolinska Institutet