Transethnic and race-stratified genome-wide association study of fibroid characteristics in African American and European American women

Objective To identify, through genome-wide association studies, genetic loci that associate with differences in fibroid size and number in a population of African American and European American women. Design Cross-sectional study. Setting Not applicable. Patient(s) Using BioVU, a clinical population from the Vanderbilt University Medical Center, and the Coronary Artery Risk Development in Young Adults cohort, a prospective cohort, we identified 1520 women (609 African American and 911 European American) with documented fibroid characteristics. Intervention(s) None. Main Outcome Measure(s) Outcome measurements include volume of largest fibroid, largest fibroid dimension, and number of fibroids (single vs. multiple). Result(s) In race-stratified analyses we achieved genome-wide significance at a variant located between MAT2B and TENM2 (rs57542984, β = 0.13; 95% confidence interval 0.09, 0.17) for analyses of largest fibroid dimension in African Americans. The strongest signal for transethnic analyses was at a variant on 1q31.1 located between PLA2G4A and BRINP3 (rs6605005, β = 0.24; 95% confidence interval 0.15, 0.33) for fibroid volume. Results from MetaXcan identified an association between predicted expression of the gene ER degradation enhancing alpha-mannosidase like protein 2 ( EDEM2 ) in the thyroid and number of fibroids ( Z score = −4.51). Conclusion(s) This study identified many novel associations between genetic loci and fibroid size and number in both race-stratified and transethnic analyses. Future studies are necessary to further validate our study findings and to better understand the mechanisms underlying these associations.