Electronic Theses and Dissertations

Rutu Rathod

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Hongmei Zhang

Committee Member

Fawaz Mzayek

Committee Member

Meredith Ray

Committee Member

Hasan Arshad

Abstract

Myocardial Infarction (MI) is one of the most common cardiac conditions in older adults. As the pathophysiological processes underlying human diseases are complex, I utilized all available data to predict the incidence of future MI using exploratory factor analysis. Six factors were identified, each representing a unique risk dimension based on loaded observed variables, e.g., the hemodynamic factor loaded systolic, diastolic blood pressure, and heart rate variables. Four factors (hemodynamic, smoking, blood lipids, and alcohol consumption) were detected as risk factors for future MI. The burden of chronic conditions among children and adolescents is increasing and one of its risk factors is obesity. Recently, DNA methylation (DNAm) at cytosine-phosphate-guanine sites (CpGs) have been shown to be associated with body mass index (BMI). I identified 204 BMI-associated CpGs with consistent DNAm between birth and 18 years, and these CpGs can serve as potential epigenetic markers of later-life BMI. Further assessment indicated that DNAm at some of these CpGs was possibly a consequence of variations in maternal BMI, birth weight, or genetic variants. We have previously demonstrated that subjects with high BMI have a high risk of asthma. I further evaluated whether DNAm mediates the association of BMI trajectories before adolescence with asthma incidence in early adulthood. Four CpGs were identified with two CpGs as potentially protective sites for asthma acquisition. Observing the close connection between obesity and lung function decline, I also examined whether DNAm mediates the association of pre-adolescent BMI trajectories with post-adolescent and adulthood lung function measures. DNAm at 8 CpGs in males and 16 CpGs in females (no overlapping) were identified as mediators. For people with high BMI trajectory, high DNAm at all the CpGs identified in males were potentially risk factors, while for females most of the CpGs were protective from lung function decline. The assessment of biological relevance of the identified consistent and mediating CpGs in aims 2-4 revealed a potential epigenetic regulatory functionality on risk of asthma and lung function through modulation of expression of their mapped and neighboring genes.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Open Access

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