Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection Barturen, Guillermo Carnero Montoro, Elena Martínez Bueno, Manuel Alcántara Domínguez, Clara Alarcón Riquelme, Marta Eugenia SARS-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. DNAmethylation 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 andmediated by genetic loci.We find an environmental trait-related signature that discriminatesmild 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. 2022-09-22T12:25:26Z 2022-09-22T12:25:26Z 2022-08-06 journal article Barturen, G... [et al.]. Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection. Nat Commun 13, 4597 (2022). [https://doi.org/10.1038/s41467-022-32357-2] https://hdl.handle.net/10481/76874 10.1038/s41467-022-32357-2 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Nature