Admixture mapping of genetic variants for uterine fibroids

Uterine leiomyoma (UL) are benign neoplasms arising from the smooth muscle cells of the uterus. One of the established risk factors for UL is African American ethnicity. Studies have consistently shown that African Americans have two to three times higher risk compared with that of non-Hispanic Whites. However, there is still no adequate explanation for the higher risk among African Americans. To investigate the genetic contribution to the observed difference between the African American and European American populations, we conducted an admixture scan in 525 eligible African American women participants to the NIEHS uterine fibroid study (NIEHS-UFS). In models with no stratification, we found multiple genomic regions showing significant and suggestive evidence of association, with chromosomal band 2q32.2 at rs256552 showing the highest score (Z-score=7.86, Bonferroni adjusted P-value=5.5 × 10(-12)) consistent with the suggestive evidence reported for this genomic region in the Black Women's Health Study. However, in models stratified by the body mass index (BMI) covariate, chromosome 1q42.2 was the sole genomic region that consistently showed suggestive associations across the BMI categories tested (Z-scores ⩽-3.96, Bonferroni adjusted P-values ⩽0.107). In age-stratified models, a significant association was observed in the older category (age >40) reaching a Z-score of 6.44 (Bonferroni-adjusted P-value=1.64 × 10(-7)) at rs256552. The mean percentage of European ancestry among cases was lower than that among controls in the NIEHS-UFS study. However, our study did not show a significant association between mean percentage of European ancestry and UL.