Characterization of DNA Methylation in African Americans with Spontaneous Preterm Birth Open Access

Parets, Sasha Erin (2015)

Permanent URL:


African Americans are at increased risk for spontaneous preterm birth (PTB), but the biological mechanisms underlying PTB are not yet known. Epigenetic factors, such as DNA methylation, may provide insight into the genes that are being actively regulated in those that deliver or are delivered preterm. The objective of this study was to evaluate DNA methylation in paired maternal blood and umbilical cord blood (fetal) samples to identify patterns specific to PTB. Peripheral blood from African American women who delivered preterm (24-34 weeks) or at term (39-41weeks) was assessed for DNA methylation across the genome using the HumanMethylation450 BeadChip. In maternal samples, no sites associated after correction for multiple comparisons though 17,829 CpG sites associated with PTB (p<.05). Examination of paired samples, irrespective of PTB status, identified 5,171 CpG sites in which methylation of maternal samples predicted methylation of her respective neonate (false discovery rate (FDR)<.05). The majority of correlated CpG sites could be attributed to one or more nearby genetic variants. However, correlated CpG sites were significantly more likely to be in genes involved in metabolic, cardiovascular and immune pathways, suggesting a role for genetic and environmental contributions to PTB risk. The observation that maternal epigenetic differences predict fetal methylation may provide insight into the heritability of PTB. In umbilical cord blood samples, we identified ~10,000 CpG sites that associate with gestational age (GA), only 29 of which associated with PTB when controlling for GA, suggesting that the majority of CpG sites primarily reflect developmental differences between preterm and term samples. In order to assess the association of DNA methylation with childhood outcomes, we investigated DNA methylation of calcitonin (CALCA), which associated with GA in cord blood and PTB in maternal blood. DNA methylation of CALCA did not associate with or mediate the relationship between maternal depressive symptoms, a known risk factor for PTB and internalizing behavioral in childhood. These finding show the importance of DNA methylation in understanding the risk and consequences of PTB in African Americans.

Table of Contents

Chapter 1: Preterm Birth and Its Long-Term Effects: Methylation to Mechanisms 1

Introduction 2

Overview of Pregnancy 3

Types of Preterm Birth 4

Proposed Mechanisms of PTB 6

Consequences of PTB 9

DNA Methylation Studies of PTB 10

DNA Methylation Studies of Long Term Outcomes of PTB 13

Opportunities for Epigenetic Studies of PTB 14

Chapter 2: DNA Methylation Provides Insight into Intergenerational Risk for Preterm Birth in African Americans 34

Introduction 35

Methods 37

Results 41

Discussion 45

References 57

Chapter 3: Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age 67

Introduction 68

Methods 69

Results 73

Discussion 77

References 89

Chapter 4: Fetal DNA Methylation of Calcitonin (CALCA) Does Not Associate with Behavioral and Cognitive Outcomes in Childhood 97

Introduction 98

Methods 100

Results 103

Discussion 105

References 111

Chapter 5: A Pilot Study of DNA Methylation in Spontaneous Preterm Birth: Conclusions & Recommendations for Future Studies 116

References 123

About this Dissertation

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
Subfield / Discipline
  • English
Research Field
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files