Researchers will study genetic differences in uterine fibroid development between Nigerian women and U.S. Black women with a $3.2 million grant awarded to Vanderbilt University Medical Center and Nigeria’s Aminu Kano Teaching Hospital (AKTH).
The research team will analyze existing genome-wide association study (GWAS) data and RNA sequencing to compare fibroid development patterns between the two populations. The highly heritable condition has been previously linked to African ancestry, with risk levels varying across different regions of Africa. Nigerian ancestry comprises a significant portion of the African American genome.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health-funded study will examine epigenetic changes in uterine fibroids, which are benign tumors that affect 77% of American women. Black women face double the risk of white women for developing fibroids.
“This study has the potential to make a significant impact on the understanding of fibroid etiology in African ancestry populations. We hope this will be the first of many collaborative grants with AKTH focused on gynecologic health,” said Digna Velez Edwards, PhD, MS, professor of Obstetrics and Gynecology at VUMC and a co-principal investigator.
Velez Edwards, who holds the Lucius E. Burch Chair of Reproductive Physiology and Family Planning, is co-principal investigator alongside VUMC’s Todd Edwards, PhD, associate professor of Medicine, and Aminu Zakari Mohammed, MBBS, professor of Pathology at Bayero University and pathologist at AKTH.
Despite the high heritability of fibroids, the understanding of the role of genetic changes in reproductive cells (germline variants) in their development is limited. Recent findings have uncovered specific variants associated with increased risk. Black women are more prone to develop fibroids at younger ages with attendant health complications. Although fibroids have a significant impact and present notable disparities among Black women, there has been relatively little progress in research and treatment compared to other complex diseases, said Velez Edwards.
Several large-scale GWAS have identified multiple fibroid risk locations in the human genome. However, the mechanisms by which these genes function in the uterus or fibroid tumors remain undefined. The study will use bulk RNA sequencing and single-cell RNA sequencing of 1,000 uterine samples to understand how GWAS-identified locations function in fibroid risk in African ancestry women. Understanding these mechanisms is essential for developing targeted therapies and management strategies for affected women.
“This large-scale population-based study will contribute to elucidation of putative functional genetic loci associated with fibroid etiology among Black women, the role of African genetic ancestry and the impact of fibroids in Africa, particularly in Nigeria with the largest global population of Black people,” said Mohammed. “It will facilitate the development of an efficient and cost-effective means of genetic diagnosis of the condition, prediction of genetic risks, and preventive strategies that will reduce the incidence and/or morbidity of fibroids.”
Researchers will also perform low-pass sequencing using whole blood samples. By utilizing overlapping samples from age-matched Black women in the U.S., researchers will identify cell-specific gene expression patterns unique to normal and fibroid tissues in women of African ancestry. This data will aid in creating a uterine tissue eQTL atlas (a resource detailing chromosomal regions of genetic variants) and gene expression prediction models. A multistage association analysis of predicted gene expression, leveraging GWAS summary statistics and data, will help identify functional regions linked to fibroid determinants and contribute to developing a uterine tissue gene expression reference specific to Black women.
This study leverages VUMC’s extensive research infrastructure, including state-of-the-art tissue facilities and expertise in -omics technologies, in addition to strong and long-standing Nigeria partnerships. These resources will be instrumental in learning more about the impact of altered gene expression on uterine fibroid risk in African ancestry populations. The findings of this study could lead to more effective prevention and treatment strategies, particularly benefiting African American women who are at a higher risk of developing fibroids.
Study co-investigators include VUMC’s Muktar Aliyu, MD, DrPH, MPH, director of the Vanderbilt Institute for Global Health and professor of Health Policy and Medicine; Zubairu Iliyasu, MBBS, MPH, PhD, professor, Aminu Kano Teaching Hospital and Bayero University, Kano, Nigeria; Ken Lau, PhD, associate professor of Cell and Developmental Biology, Vanderbilt University School of Medicine; and Scott Williams, PhD, professor, Department of Genetics and Genome Sciences, Case Western Reserve University. Aliyu holds the Directorship in Global Health.
This study is funded by grant R01HD112169.
