Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection
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AuthorBarturen, Guillermo; Carnero Montoro, Elena; Martínez Bueno, Manuel; Alcántara Domínguez, Clara; Alarcón Riquelme, Marta Eugenia
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]
SponsorshipConsejeria de Transformacion Economica, Industria, Conocimiento y Universidades of the regional government of Andalucia; European Union through European Regional Development Fund CV20-10150; Consejo Superior de Investigaciones cientificas CSIC-COV19-016/202020E155; Junta de Castilla y Leon COVID 07.04.467B04.74011.0; Consejeria de Salud y Familias of the regional government of Andalucia PECOVID-0072-2020; Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry) through the Sara Borrell subprogram CD18/00153; Programa Estrategico Instituto de Biologia y Genetica Molecular, IBGM excellence programme CLU-2029-02 CCVC8485
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.