Exploring the Role of Genetics and Epigenetics in the Response to Conflict-Related Violence
General Material Designation
[Thesis]
First Statement of Responsibility
Clukay, Christopher J.
Subsequent Statement of Responsibility
Mulligan, Connie J.
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
University of Florida
Date of Publication, Distribution, etc.
2020
GENERAL NOTES
Text of Note
162 p.
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
University of Florida
Text preceding or following the note
2020
SUMMARY OR ABSTRACT
Text of Note
Psychosocial stress, the physical and mental stress resulting from disruptive social forces, substantially impacts human health. Within this category, exposure to conflict-related violence is particularly concerning due to its intensity and the number of people affected. In this dissertation, I explore how genetics may impact the human response to stress and how stress may impact epigenetic variation in two populations exposed to conflict-related violence. Genetic variation may cause differences in stress perception or response. As such, in the first study (Ch. 2 and 3), I explored the effect of genotype on the human response to psychosocial stress among Syrian refugee youth. Utilizing samples from a collaboration (n = 398), I extracted DNA and assayed for genetic variants in four candidate genes; FAAH, SLC6A4, BDNF, and COMT. Variants were tested for associations with five measures of stress and psychosocial health using longitudinal mixed effects modeling. After multiple testing correction, I observed an association between COMT genotype and perceived stress in males and interactions with resilience in association with multiple measures in females. In the second study (Ch. 4 and 5), I examined the impact of psychosocial stress on epigenetic variation, specifically DNA methylation (DNAm), and health among mother-infant dyads in the Democratic Republic of the Congo. Using principal component analysis to summarize DNAm at a given gene, I tested DNAm at methylation complex genes, whose products control genome-wide DNAm, for associations with stress, genome-wide mean methylation (GMM), and birthweight. I observed multiple associations between GMM and DNAm at methylation complex genes, suggesting that altered GMM may be linked to altered methylation complex regulation. I then analyzed DNAm throughout the genome by grouping and testing CpG sites at individual, regional, and genome-wide levels. While testing individual CpG sites revealed no significant associations with maternal stress, multiple associations were observed at regional and genome-wide levels, with responses differing between mothers and newborns. This dissertation highlights the complexities associated with the human response to stress and suggests possible molecular mechanisms related that response. It is hoped that future studies will continue to explore these effects to better understand how the environment impacts human health.