Barturen, GuillermoCarnero-Montoro, ElenaMartínez-Bueno, ManuelRojo-Rello, SilviaSobrino, BeatrizPorras-Perales, ÓscarAlcántara-Domínguez, ClaraBernardo, DavidAlarcón-Riquelme, Marta E2024-02-272024-02-272022-08-06http://hdl.handle.net/10668/19543http://hdl.handle.net/20.500.12105/18733SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases.engVoRhttp://creativecommons.org/licenses/by/4.0/COVID-19Cytokine Release SyndromeCytokinesDNA MethylationHumansSARS-CoV-2Attribution 4.0 International35933486131459710.1038/s41467-022-32357-22041-1723Nature communicationsopen access