Cargando…
Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry
Male sex and advanced age are associated with severe symptoms of COVID-19. Sex and age also exhibit substantial associations with genome-wide DNA methylation (DNAm) differences in humans. Using a random sample of Illumina EPIC-based genome-wide methylomes from peripheral whole blood of 1,976 parents...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182232/ https://www.ncbi.nlm.nih.gov/pubmed/35679253 http://dx.doi.org/10.1371/journal.pone.0269105 |
_version_ | 1784723984203382784 |
---|---|
author | Bohlin, Jon Page, Christian M. Lee, Yunsung Pettersson, John H.-O. Jugessur, Astanand Magnus, Per Håberg, Siri E. |
author_facet | Bohlin, Jon Page, Christian M. Lee, Yunsung Pettersson, John H.-O. Jugessur, Astanand Magnus, Per Håberg, Siri E. |
author_sort | Bohlin, Jon |
collection | PubMed |
description | Male sex and advanced age are associated with severe symptoms of COVID-19. Sex and age also exhibit substantial associations with genome-wide DNA methylation (DNAm) differences in humans. Using a random sample of Illumina EPIC-based genome-wide methylomes from peripheral whole blood of 1,976 parents, participating in The Norwegian Mother, Father and Child Cohort Study (MoBa), we explored whether DNAm in genes linked to SARS-CoV-2 host cell entry and to severe COVID-19 were associated with sex and age. This was carried out by testing 1,572 DNAm sites (CpGs) located near 45 genes for associations with age and sex. We found that DNAm in 281 and 231 of 1,572 CpGs were associated (p(FDR)<0.01) with sex and aging, respectively. CpGs linked to SARS-CoV-2 host cell entry genes were all associated with age and sex, except for the ACE2 receptor gene (located on the X-chromosome), which was only associated with sex (p(FDR)<0.01). Furthermore, we examined whether 1,487 autosomal CpGs associated with host-cell entry and severe COVID-19 were more or less associated with sex and age than what would be expected from the same number of randomly sampled genome-wide CpGs. We found that the CpGs associated with host-cell entry and severe COVID-19 were not more or less associated with sex (R(2) = 0.77, p = 0.09) than the CpGs sampled from random genomic regions; age was actually found to be significantly less so (R(2) = 0.36, p = 0.04). Hence, while we found wide-spread associations between sex and age at CpGs linked to genes implicated with SARS-CoV-2 host cell entry and severe COVID-19, the effect from the sum of these CpGs was not stronger than that from randomly sampled CpGs; for age it was significantly less so. These findings could suggest that advanced age and male sex may not be unsurmountable barriers for the SARS-CoV-2 virus to evolve increased infectiousness. |
format | Online Article Text |
id | pubmed-9182232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-91822322022-06-10 Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry Bohlin, Jon Page, Christian M. Lee, Yunsung Pettersson, John H.-O. Jugessur, Astanand Magnus, Per Håberg, Siri E. PLoS One Research Article Male sex and advanced age are associated with severe symptoms of COVID-19. Sex and age also exhibit substantial associations with genome-wide DNA methylation (DNAm) differences in humans. Using a random sample of Illumina EPIC-based genome-wide methylomes from peripheral whole blood of 1,976 parents, participating in The Norwegian Mother, Father and Child Cohort Study (MoBa), we explored whether DNAm in genes linked to SARS-CoV-2 host cell entry and to severe COVID-19 were associated with sex and age. This was carried out by testing 1,572 DNAm sites (CpGs) located near 45 genes for associations with age and sex. We found that DNAm in 281 and 231 of 1,572 CpGs were associated (p(FDR)<0.01) with sex and aging, respectively. CpGs linked to SARS-CoV-2 host cell entry genes were all associated with age and sex, except for the ACE2 receptor gene (located on the X-chromosome), which was only associated with sex (p(FDR)<0.01). Furthermore, we examined whether 1,487 autosomal CpGs associated with host-cell entry and severe COVID-19 were more or less associated with sex and age than what would be expected from the same number of randomly sampled genome-wide CpGs. We found that the CpGs associated with host-cell entry and severe COVID-19 were not more or less associated with sex (R(2) = 0.77, p = 0.09) than the CpGs sampled from random genomic regions; age was actually found to be significantly less so (R(2) = 0.36, p = 0.04). Hence, while we found wide-spread associations between sex and age at CpGs linked to genes implicated with SARS-CoV-2 host cell entry and severe COVID-19, the effect from the sum of these CpGs was not stronger than that from randomly sampled CpGs; for age it was significantly less so. These findings could suggest that advanced age and male sex may not be unsurmountable barriers for the SARS-CoV-2 virus to evolve increased infectiousness. Public Library of Science 2022-06-09 /pmc/articles/PMC9182232/ /pubmed/35679253 http://dx.doi.org/10.1371/journal.pone.0269105 Text en © 2022 Bohlin et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bohlin, Jon Page, Christian M. Lee, Yunsung Pettersson, John H.-O. Jugessur, Astanand Magnus, Per Håberg, Siri E. Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title | Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title_full | Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title_fullStr | Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title_full_unstemmed | Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title_short | Age and sex effects on DNA methylation sites linked to genes implicated in severe COVID-19 and SARS-CoV-2 host cell entry |
title_sort | age and sex effects on dna methylation sites linked to genes implicated in severe covid-19 and sars-cov-2 host cell entry |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182232/ https://www.ncbi.nlm.nih.gov/pubmed/35679253 http://dx.doi.org/10.1371/journal.pone.0269105 |
work_keys_str_mv | AT bohlinjon ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT pagechristianm ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT leeyunsung ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT petterssonjohnho ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT jugessurastanand ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT magnusper ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry AT habergsirie ageandsexeffectsondnamethylationsiteslinkedtogenesimplicatedinseverecovid19andsarscov2hostcellentry |