Genetic Contributions to Disparities in Preterm Birth Among African-American Women
Open Access
- Author:
- Pearson, Laurel
- Graduate Program:
- Genetics
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 01, 2012
- Committee Members:
- Mark Shriver, Dissertation Advisor/Co-Advisor
David John Vandenbergh, Committee Chair/Co-Chair
Kenneth Monrad Weiss, Committee Member
Nina G Jablonski, Committee Member
Jerome Strauss Iii, Special Member - Keywords:
- Preterm Birth
Admixture Mapping
Accelerated Evolution
African American
PPROM
Health Disparities - Abstract:
- In the United States African-American women experience the poorest pregnancy outcomes of any ethnic group. Compared to European-American women, African-American women have a substantially greater risk of preterm birth, low birth weight neonates, and infant mortality. A variety of factors have been hypothesized to contribute to disparities in these complex pregnancy phenotypes including environment, lifestyle, and genetics. This dissertation investigates genetic ancestry and the role of genes in contributing to risk of poor pregnancy outcomes among African-American women. In the first portion of this research the association between West African genomic ancestry and birth weight and the association between genomic ancestry, skin pigmentation, and serum vitamin D level were investigated. Increasing West African ancestry was found to be significantly associated with lower birth weight in female neonates and was inversely correlated with serum vitamin D level. For the next phase of this project, admixture mapping was used to identify novel regions of the genome that are associated with preterm birth due to preterm premature rupture of membranes (PPROM). In this case-control analysis of African-American neonates, regions on five chromosomes (5, 8, 11, 19, and 21) were identified to be associated with increased risk. These regions provide areas for future research into the genetic contributions to risk of preterm birth due to PPROM. In the final portion of this research, 90 previously reported preterm birth candidate genes were tested for signatures of accelerated evolution. Using three test statistics in the parental populations that contribute to African-American admixture, European and West African, forty-four of the preterm birth candidate genes had evidence of non-neutral evolution. This analysis helped prioritize genes that are more likely to contribute to the increased risk of preterm birth in African-American women compared to European-American women. Future work will include a replication of the admixture mapping study to refine the chromosomal regions found to be associated with risk of preterm birth due to PPROM. Additionally, genotyping of the forty-four preterm birth candidate genes nominated by the three tests for accelerated evolution is planned to look for risk alleles that contribute to the disparity in preterm birth among African-American women.