Objective-To investigate UL incidence in relation to polymorphisms in genes involved in vitamin D metabolism and skin pigmentation. Rates of uterine leiomyomata (UL) are 2-3 times higher in African Americans than European Americans. Recent studies suggest that vitamin D deficiency is associated with an increased risk of UL.Design-Nested case-control study. Setting-BlackWomen's Health Study, a prospective cohort study of African American women. Patient(s)-2,232premenopausal women diagnosed with UL confirmed by ultrasound or surgery during 1997-2011 (cases) and 2,432 premenopausal women never diagnosed with UL through 2011 (controls). Intervention-None.Main outcome measure-Self-reported UL. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between each polymorphism and UL, controlling for age, geographic region, and ancestry.Results-Three of twelve polymorphisms were associated with UL at the nominal significance level: rs4944957 and rs12800438 near DHCR7, and rs6058017 in ASIP. After correction for multiple hypothesis testing, two SNPs remained significantly associated with UL (rs12800438 and rs6058017). Compared with the AA genotype for rs12800438 (correlated with higher serum 25(OH)D levels), ORs were 1.09 (95% CI: 0.92, 1.29) and 1.23 (95% CI: 1.03, 1.47) for the GA and GG genotypes, respectively. Compared with the AA genotype for rs6058017 (correlated with higher serum 25(OH)D levels), ORs were 1.01 (95% CI: 0.83, 1.22) and 1.18 (95% CI: 0.97, 1.44) for the GA and GG genotypes, respectively. Conclusions-Our data support the hypothesis that vitamin D deficiency is involved in UL etiology.