Author ORCID Identifier
0000-0003-0888-5272
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Human and Molecular Genetics
First Advisor
Timothy P. York, Ph.D
Second Advisor
Bradley Todd Webb, Ph.D
Third Advisor
Hermine Maes, Ph.D
Fourth Advisor
Kimberly Jefferson, Ph.D
Fifth Advisor
John Quillin, Ph.D
Abstract
This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. Significant genetic correlations between cervical change and the length of pregnancy ( |rg | ≥ 0.49) suggest that many of the genes influencing cervical shortening also influence the timing of birth, hinting at biological mechanisms and genetic risk factors that may be shared between these traits. Exploratory analyses have identified potentially relevant associations between cervical shortening and genes involved in progesterone, estrogen, relaxin, and insulin signaling—key hormonal pathways involved in pregnancy maintenance and the timing of delivery. Furthermore, this study demonstrates how polygenic profiles can help identify women who are more likely to develop a short cervix during pregnancy, a primary risk factor for preterm birth that can be effectively managed with timely clinical interventions. Despite its relatively small sample size, this project has produced compelling results, and is currently the largest genetic study of pregnancy in Black/African American women. We hope that the results of this study could one day improve prenatal care for Black women, who are disproportionately affected by preterm birth and significantly underrepresented in genetic and clinical research.
Rights
© Hope M. Wolf
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-11-2024
Included in
Biostatistics Commons, Genetics Commons, Longitudinal Data Analysis and Time Series Commons, Obstetrics and Gynecology Commons, Statistical Models Commons, Women's Health Commons