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. 2021 Jul 31;12(8):1198.
doi: 10.3390/genes12081198.

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Rutu Rathod  1 , Aniruddha Rathod  1 , Parnian Kheirkhah Rahimabad  1 , Jiasong Duan  1 , Hongmei Zhang  1 , S Hasan Arshad  2   3   4 , Wilfried Karmaus  1
Affiliations

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Rutu Rathod et al. Genes (Basel). .

Abstract

DNA methylation (DNAm) patterns over time at 1146 CpGs on coronavirus-related genes were assessed to understand whether the varying differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults could be explained through epigenetic alterations in a host cell's transcriptional apparatus to coronaviruses. DNAm data from the Isle of Wight birth cohort (IOWBC) at birth, 10, 18, and 26 years of age were included. Linear mixed models with repeated measurements stratified by sex were used to examine temporal patterns, and cluster analysis was performed to identify CpGs following similar patterns. CpGs on autosomes and sex chromosomes were analyzed separately. The association of identified CpGs and expression of their genes were evaluated. Pathway enrichment analyses of the genes was conducted at FDR = 0.05. DNAm at 635 of the 1146 CpGs on autosomes showed statistically significant time effects (FDR = 0.05). The 635 CpGs were classified into five clusters with each representing a unique temporal pattern of DNAm. Of the 29 CpGs on sex chromosomes, DNAm at seven CpGs in males and eight CpGs in females showed time effects (FDR = 0.05). Sex-specific and non-specific associations of DNAm with gene expression were found at 24 and 93 CpGs, respectively. Genes which mapped the 643 CpGs represent 460 biological processes. We suggest that the observed variability in DNAm with advancing age may partially explain differing susceptibility, disease severity, and mortality of coronavirus infections among different age groups.

Keywords: COVID-19; DNA methylation; IoW cohort; SARS-CoV2; coronavirus; epigenetics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
DNA methylation profiles of the five CpG clusters represented by the median of gender and cell type heterogeneity adjusted DNA methylation at each age.
Figure 2
Figure 2
DNA methylation patterns of the available CpGs on sex chromosomes in males and females represented by cell type adjusted DNA methylation over time. The solid lines represent temporal patterns of CpGs on gene ACE2 and dash-dotted lines are for CpGs on gene CD40LG.
See this image and copyright information in PMC

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