Author ORCID Identifier

0000-0001-8169-9754

Defense Date

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Human Genetics

First Advisor

Dr. Timothy P. York

Second Advisor

Dr. Roxann Roberson-Nay

Abstract

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six times across pregnancy and the first year postpartum as part of the Pregnancy, Race, Environment, Genes (PREG) Study. Statistical analyses were completed using a combination of the R statistical environment, Bioconductor packages, MplusAutomate, and Mplus software. Prenatal maternal DNAm was measured using the Infinium HumanMethylation450 Beadchip. Latent growth curve models were used to analyze repeated measures of maternal DNAm and to quantify site-level DNAm latent trajectories over the course of pregnancy. The purpose was to characterize the location and nature of prenatal DNAm changes and to test the influence of clinical and demographic factors on prenatal DNAm remodeling. Results. Over 1300 sites had DNAm trajectories significantly associated with either maternal age or lifetime MD. Many of the genomic regions overlapping significant results replicated previous age and MD-related genetic and DNAm findings. Discussion. Future work should capitalize on the progress made here integrating structural equation modeling (SEM) with longitudinal omics-level measures.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-6-2019

Available for download on Sunday, August 04, 2024

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