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

Rutu Rathod,Wilfried Karmaus,Jiasong Duan,Aniruddha Rathod,S Hasan Arshad,Parnian Kheirkhah Rahimabad,Hongmei Zhang

doi:10.3390/genes12081198

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.

Highlights

Coronaviruses are a group of zoonotic pathogens that were previously considered to cause relatively benign infections in humans [1]
Given the dynamic nature of DNA methylation (DNAm) during aging and its potential role in coronavirus infection, we suggest that changes in DNAm over time could explain the differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults
We examined the development of methylation levels of CpGs potentially associated with coronavirus infection using four measurements spanning from birth to age 26 years

Summary

Introduction

Coronaviruses are a group of zoonotic pathogens that were previously considered to cause relatively benign infections in humans [1]. East respiratory syndrome coronavirus (MERS-CoV) in 2012 in Middle Eastern countries, proved coronaviruses’ ability to cause severe respiratory disorders [1]. Epidemiological studies have shown a significant difference between adult and pediatric populations in terms of incidence and symptomatology of SARS-CoV-2 infection. Children seem to be less susceptible to develop the disease and are more likely to present with milder symptoms if infected, while adult subjects are prone to develop severe forms with higher mortality rates [3]. Studies on SARS and MERS infections show a similar trend of milder symptoms and lower mortality rates in children compared to adults [10,11]. Children and adults have shown different distribution and functioning of angiotensin-converting enzyme-2 (ACE2), the receptor coded on the X-chromosome and used by the SARS virus, SARS-CoV-2, and human coronavirus-NL63 (HCoV-NL63) [12]. Cellular and molecular components, of both the innate and adaptive immune systems, and their ability to coordinate an effective immune response deteriorates drastically with age, explaining poorer outcomes in the elderly [13]

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