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Home > Graduate School > Theses and Dissertations > 7894
Theses and Dissertations
The genetic architecture of cervical change during pregnancy: from modeling to mechanism — does the cervix mediate maternal risk for spontaneous preterm birth.
Hope M. Wolf , Virginia Commonwealth University Follow
Author ORCID Identifier
0000-0003-0888-5272
Defense Date
Document type.
Dissertation
Degree Name
Doctor of Philosophy
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
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.
© Hope M. Wolf
VCU University Archives
VCU Theses and Dissertations
Date of Submission
Since December 16, 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
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See the VCU Libraries Dissertations Research Guide for information on submitting your ETD, accessing older dissertations from VCU, and finding dissertations from other universities. The majority of VCU theses and dissertations may be found in Special Collections and Archives at James Branch Cabell Library or the Health Sciences Library.
Electronic theses and dissertations make VCU student research and creativity available online as full-text documents and multimedia presentations for use by the university community and others involved in research. The thesis and dissertation manual provides a general set of guidelines approved by the University Graduate Council. However, the ...
Dec 2, 2024 · You can purchase copies of dissertations through UMI, the producer of Dissertation Abstracts (also known as Dissertations and Theses Full Text). Submit your order online or print out a form to mail or fax. Note that the order form allows you to search for dissertations by author or title.
The VCU Graduate School thesis and dissertation website, as developed by the University Graduate Council and VCU Libraries, serves as a guide for the preparation of electronic graduate theses and dissertations for graduate students in all programs within the university.
Submission Guidelines for Theses and Dissertations. 1. Make sure your electronic thesis or dissertation (ETD) is in a recommended format, as listed as About Scholars Compass. PDF is preferred. 2. Write an abstract for your ETD. Please also select keywords. These are words that will help a user locate your ETD through a search. 3.
Dec 2, 2024 · VCU has been accepting ETD's on a pilot and voluntary basis since 2002. As of fall 2009, students are required to submit their theses or dissertations electronically to the Graduate School. VCU's theses and dissertations are records of permanent, enduring value and will remain available indefinitely.
The VCU Graduate School Electronic Thesis and Dissertation manual provides a general set of guidelines approved by the University Graduate Council. However, the student's thesis/dissertation committee is the final arbiter concerning the thesis/dissertation's final acceptability. The committee's
Sep 6, 2023 · VCU Libraries provides access to the electroniic full-test versions of nearly all dissertations published in the U.S. since 1997 through this database. You can search it directly from this page or access it from the Databases A-Z (D) list on the VCU Libraries' homepage (www.library.vcu.edu). Dissertations and Theses Full Text (Proquest) Search ...
VCU Theses and Dissertations. Date of Submission. 12-11-2024. Additional Files. Wolf_Hope_Supplemental_Materials_PhD.pdf (364 kB) Download DOWNLOADS. Since December ...
• Final defense of thesis/dissertation • ETD approval form with all approval signatures, including the graduate dean’s and, if applicable, documentation of IRB or IACUC approval number • Submission of the ETD to the VCU Scholar’s Compass according to instructions in the VCU Graduate School thesis and dissertation manual (http ...