Electronic Theses and Dissertations

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Hongmei Zhang

Committee Member

Wilfried Karmaus

Committee Member

Fawaz Mzayek

Committee Member

John Holloway

Abstract

Asthma is a global public health concern with limited preventive strategies. Recently, DNA methylation (DNAm) has been studied to understand the underlying pathogenesis of asthma. The role of DNAm in asthma acquisition from pre- to post- adolescence is unclear, and how its role changes from adolescence to adulthood is also unknown. The studies in this dissertation were carried out using data in two birth cohorts with one as a discovery cohort and the other as replication cohort. Longitudinal assessments in both cohorts revealed that the associations of DNAm at 62 Cytosine-Guanine sites (CpG sites) with asthma acquired during adolescence were different from those with asthma acquired in young adulthood since post-adolescence. Asthma can be atopic and non-atopic, and their underlying mechanisms are likely to be different in terms of DNAm markers. To this end, I further examined the mediating role of atopy in childhood on the association of DNAm in newborns with childhood asthma acquisition. I identified 30 CpGs that showed only indirect effects, i.e., DNAm in newborns at these CpGs might play a role in the development of atopic asthma with atopy being a mediator. Also, I found 103 CpGs showing only direct effects, which may contribute to the occurrence of non-atopic asthma. Asthma and rhinitis commonly coexist and share common biomarkers. I examined CpGs in newborns for their association in DNAm with these two allergic conditions during pre-adolescence. I detected 133 CpGs at birth that were associated with preadolescent asthma and/or rhinitis in both cohorts. Further, for all the studies, pathway enrichment analyses were conducted to understand the biological functionality of the identified CpGs. Additionally, biological relevance of the CpGs showing consistent findings between the two cohorts was evaluated using gene expressions. Findings from this dissertation will help identify epigenetic biomarkers for asthma acquisition and coexisting asthma and/or rhinitis as well as understand the underlying pathogenesis of these conditions. More importantly, it will benefit our future efforts in allergic disease prediction and consequently prevention of these common allergic conditions.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

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