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.