Maternal SARS-CoV-2 exposure alters infant DNA methylation

Autor: Rachel A. Hill, Andrew Gibbons, Uni Han, Wittaya Suwakulsiri, Angela Taseska, Fleur Hammet, Melissa Southey, Atul Malhotra, Michael Fahey, Kirsten R. Palmer, Rod W. Hunt, Izaak Lim, Vesna Newman-Morris, Suresh Sundram
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Brain, Behavior, & Immunity - Health, Vol 27, Iss , Pp 100572- (2023)
Druh dokumentu: article
ISSN: 2666-3546
DOI: 10.1016/j.bbih.2022.100572
Popis: Background: Infection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred in utero to offspring. We hypothesised that in utero exposure to SARS-CoV-2 in humans may alter infant DNA methylation, particularly in genes associated with neurodevelopment. We aimed to test this hypothesis in a pilot sample of children in Victoria, Australia, who were exposed in utero to SARS-CoV-2. Methods: DNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2 in utero exposed and (n = 4) non-exposed infants and methylation status assessed across 850,000 methylation sites using an Illumina EPIC BeadChip. We also conducted an exploratory enrichment analysis using Gene Ontology annotations. Results: 1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value
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