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

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years.
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DOI:
10.3390/genes12081198
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发表时间:
2021-07-31
期刊:
影响因子:
3.5
通讯作者:
Karmaus W
Karmaus W
中科院分区:
生物学3区
文献类型:
--
作者:
Rathod R;Rathod A;Rahimabad PK;Duan J;Zhang H;Arshad SH;Karmaus W

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对冠状病毒相关基因上1146个CpG的DNA甲基化(DNAm)模式随时间的变化进行了评估,以了解儿童和年轻人SARS-CoV-2感染的易感性,症状和结果的不同差异是否可以通过宿主细胞对冠状病毒转录装置的表观遗传改变来解释。包括出生时、10岁、18岁和26岁时来自怀特岛出生队列(IOWBC)的DNA m数据。使用按性别分层的重复测量的线性混合模型来检查时间模式,并进行聚类分析以确定遵循相似模式的CpG。分别分析常染色体和性染色体上的CpG。评估鉴定的CpG与其基因表达的关联。在FDR = 0.05下进行基因的途径富集分析。常染色体上1146个CpG中的635个处的DNAm显示出统计学显著的时间效应(FDR = 0.05)。将635个CpG分为五个簇,每个簇代表DNAm的独特时间模式。在性染色体上的29个CpG中,男性中7个CpG和女性中8个CpG的DNAm表现出时间效应(FDR = 0.05)。性别特异性和非特异性协会的DNAm与基因表达被发现在24和93个CpG,分别。映射643个CpG的基因代表460个生物过程。我们认为,随着年龄的增长,观察到的DNAm的变异性可能部分解释了不同年龄组之间冠状病毒感染的不同易感性,疾病严重程度和死亡率。
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.
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