%0 Journal Article
%A Pietzner, Maik
%A Chua, Robert Lorenz
%A Wheeler, Eleanor
%A Jechow, Katharina
%A Willett, Julian D. S.
%A Radbruch, Helena
%A Trump, Saskia
%A Heidecker, Bettina
%A Zeberg, Hugo
%A Heppner, Frank L.
%A Eils, Roland
%A Mall, Marcus A.
%A Richards, J. Brent
%A Sander, Leif-Erik
%A Lehmann, Irina
%A Lukassen, Sören
%A Wareham, Nicholas J.
%A Conrad, Christian
%A Langenberg, Claudia
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19 : 
%U https://hdl.handle.net/21.11116/0000-000B-0F3F-0
%R 10.1038/s41467-022-31999-6
%7 2022-08-15
%D 2022
%8 15.08.2022
%* Review method: peer-reviewed
%X Genetic factors have been found to be associated with severe COVID-19. Here, the authors integrated genomic, proteomic, and single-cell data to identify ELF5 as a candidate risk gene with a possible role in respiratory epithelial cells, which are targeted by SARS-CoV-2.<br><br>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 x 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.
%K Genetic association study,  Molecular medicine,  Risk factors, Viral infection

%J Nature Communications
%V 13
%] 4484
%@ 2041-1723