% pubman genre = article
@article{item_3407417,
title = {{ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19}},
author = {Pietzner, Maik and Chua, Robert Lorenz and Wheeler, Eleanor and Jechow, Katharina and Willett, Julian D. S. and Radbruch, Helena and Trump, Saskia and Heidecker, Bettina and Zeberg, Hugo and Heppner, Frank L. and Eils, Roland and Mall, Marcus A. and Richards, J. Brent and Sander, Leif-Erik and Lehmann, Irina and Lukassen, S{\"o}ren and Wareham, Nicholas J. and Conrad, Christian and Langenberg, Claudia},
issn = {2041-1723},
doi = {10.1038/s41467-022-31999-6},
year = {2022},
abstract = {{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.{\textless}br{\textgreater}{\textless}br{\textgreater}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 {\textgreater}4-fold higher risk (odds ratio: 4.88; 95{\textpercent}-CI: 2.47-9.63; p-value {\textless} 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.}},
journal = {{Nature Communications}},
volume = {13},
eid = {4484},
}