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1.	Niemi, MEK, et al. (author) 2021 swepub:Mat__t
2.	Kanai, M, et al. (author) 2023 swepub:Mat__t
3.	Pietzner, M, et al. (author) ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19 2022 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4484- Journal article (peer-reviewed)abstract 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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Type of publication: journal article (1)

Type of content: peer-reviewed (1)

Author/Editor: Brown, J. (2); Clark, A. (2); Cole, S. (2); Davies, M. (2); Endo, M. (2); Erdmann, J. (2); show more...; Fox, H. (2); Hasegawa, Y. (2); Hughes, G. (2); Jackson, M. (2); Jackson, P. (2); Karthik, K. (2); Lee, H. (2); Lewis, A. (2); Maeno, T. (2); Saleem, M. (2); Suzuki, Y. (2); Walker, R. (2); White, S. (2); Williams, S. (2); Wilson, A. (2); Wright, M. (2); Wu, Y. (2); Yamada, M. (2); Nagata, K. (2); Davidson, N. (2); Dobson, E. (2); Harvey, A. (2); Lange, C. (2); Oliveira, M. (2); Rose, A. (2); Davies, E. (2); Grau, N. (2); Haider, S. (2); Tokunaga, K. (2); Suzuki, S (2); Gupta, A. (2); Robinson, M. (2); Dennis, C. (2); Marshall, R. (2); Smith, M. (2); Martin, J. (2); Mbarek, H (2); Davies, G (2); Harris, C (2); Kumar, S (2); Brown, A. (2); Brown, E. (2); Clark, M. (2); Hays, C. (2); show less...

University: Karolinska Institutet (2)

Language: English (3)

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