Investigating susceptibility to Covid-19 and other health conditions through epigenetic epidemiology

Abstract

Epigenetics is defined as heritable changes in gene expression that occur independently of changes to the genetic code. This thesis explores DNA methylation changes in humans that arise in different environmental conditions using computational tools in two different projects.

In the first project, an EWAS of differential methylation between hospitalised and non-hospitalised COVID-19 patients was conducted as part of the COVRES study. A novel aspect of this study was the use of saliva as the sample tissue, as the respiratory tract is the site of SARS-CoV-2 infection and most comparable studies have been conducted in blood. Significant differential methylation at genes related to cardiac function and viral response were identified; a particularly novel finding was the discovery of highly significant differential methylation at a type III interferon region. The most significant differentially methylated genes were also interpreted in the light of transcriptomic and genomic differences between the groups. Furthermore, epigenetic age acceleration assessments were carried out, in addition to assessments of methylation smoking score and other clinical variables. Significant epigenetic age acceleration in the hospitalised COVID-19 patients was discovered.

The second project examines effects of folic acid supplementation on DNA methylation in maternal blood during the second and third trimesters of pregnancy as part of the EpiFASSTT study. An epigenome-wide association study (EWAS) of supplement-treated and placebo-treated mothers was conducted at two different time points. This investigation uncovered differential methylation in genes related to cognition and development among placebo-treated mothers, which were validated in an independent cohort.

Additionally, a review of two popular pipelines for DNA methylation microarray analysis was conducted. Overall, in this thesis, computational tools were utilised to analyse DNA methylation data, culminating in novel insights into the epigenetic effects of folic acid supplementation and COVID-19 disease processes in two separate projects.

Thesis is embargoed until 31st August 2028

Date of Award	Aug 2026
Original language	English
Sponsors	Department for the Economy (Northern Ireland)
Supervisor	Colum Walsh (Supervisor), Rachelle Irwin (Supervisor) & David Gibson (Supervisor)