Electronic Theses and Dissertations

Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Wilfrie Karmaus

Committee Member

Hongmei Zhang, Fawaz Mzayek, Yu Jiang

Abstract

Studies demonstrated genetic and epigenetic associations with eczema. However, not many studies investigated the interaction of epigenetic and genetic associations with eczema. Additionally, few studies examined gene expression (GE) levels along with epigenetic and genetic associations with eczema. Using the multigenerational epigenetic, genetic, and GE data of Isle of Wight (IOW) birth cohort, I investigated the interplay between DNA methylation (DNAm) and a genetic variant (SNP) with eczema and GE. First, I evaluated epigenome-wide associations of eczema using the DNAm data of two generations of the IOW (namely, the F1 and F2 generations) and examined the overlap of genes of significant CpG sites with the genes associated with eczema in prior research. Minimal overlap was found between the genes based on this study and prior published studies. Next, I investigated whether the interaction between DNAm and SNP modifies the risk of eczema focusing on TSLP. Increased risk of eczema was observed to be associated with interactions of DNAm at cg08354104 with AA, AG genotypes of rs3806933 compared to interaction of cg08354104 with GG genotype of rs3806933 in F1 and F2 generations. However, interactions of DNAm at cg15089387 with AA, AG genotypes of rs1837253 showed protective effects in F2 generation (infancy) but were associated with risk in F1 generation (1-2 to 18 years) compared to the interaction of cg15089387 and GG genotype of rs1837253. Hence, for this epigenetic marker, there is no replication. Finally, I investigated whether the effect of the interaction of DNAm and SNP of the TSLP gene on eczema was mediated via GE of TSLP using path analysis. Interactions of DNAm of cg18897025 with rs3806933 were found to be associated with GE and the risk of eczema. The mediation analysis was only tested in the F2. More studies are needed to test this link in an independent cohort. The effect of the interaction of DNAm with SNP of TSLP (cg08354104 and rs3806933) on the risk of eczema was identified and replicated in two generations of IOW. It will be strategically informative to test such associations for other eczema-associated genes.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

Embargoed until 11/15/2024

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