Uterine fibroids disproportionately impact Black women. Evidence suggests Black women have earlier onset and higher cumulative risk. This risk disparity may be due an imbalance of risk alleles in one parental geographic ancestry subgroup relative to others. We investigated ancestry proportions for the 1000 Genomes phase 3 populations clustered into six geographic groups for association with fibroid traits in Black women (n = 583 cases, 797 controls) and White women (n = 1195 cases, 1164 controls). Global ancestry proportions were estimated using ADMIXTURE. Dichotomous (fibroids status and multiple fibroid status) and continuous outcomes (volume and largest dimension) were modeled for association with ancestry proportions using logistic and linear regression adjusting for age. Effect estimates are reported per 10% increase in genetically inferred ancestry proportion. Among Black women, West African (WAFR) ancestry was associated with fibroid risk, East African ancestry was associated with risk of multiple fibroids, Northern European (NEUR) ancestry was protective for multiple fibroids, Southern European ancestry was protective for fibroids and multiple fibroids, and South Asian (SAS) ancestry was positively associated with volume and largest dimension. In White women, NEUR ancestry was protective for fibroids, SAS ancestry was associated with fibroid risk, and WAFR ancestry was positively associated with volume and largest dimension. These results suggest that a proportion of fibroid risk and fibroid trait racial disparities are due to genetic differences between geographic groups. Further investigation at the local ancestry and single variant levels may yield novel insights into disease architecture and genetic mechanisms underlying ethnic disparities in fibroid risk.

子宫肌瘤不成比例地影响黑人女性。有证据表明，黑人女性发病较早，累积风险较高。这种风险差异可能是由于一个亲本地理祖先亚组中的风险等位基因相对于其他亚组的不平衡。我们调查了 1000 个基因组 3 期人群的血统比例，这些人群分为六个地理组，与黑人女性（n  = 583 例，797 名对照）和白人女性（n = 1195 例，1164 例对照）。使用 ADMIXTURE 估计全球血统比例。使用根据年龄调整的逻辑回归和线性回归对二分类（肌瘤状态和多发性肌瘤状态）和连续结果（体积和最大尺寸）进行建模，以与祖先比例相关联。遗传推断的血统比例每增加 10%，就会报告影响估计值。在黑人女性中，西非（WAFR）血统与肌瘤风险相关，东非血统与多发性肌瘤风险相关，北欧（NEUR）血统对多发性肌瘤具有保护作用，南欧血统对肌瘤和多发性肌瘤具有保护作用，南亚（SAS）血统与体积和最大尺寸呈正相关。在白人女性中，NEUR 血统对肌瘤有保护作用，SAS 血统与肌瘤风险相关，而 WAFR 血统与体积和最大尺寸呈正相关。这些结果表明，部分肌瘤风险和肌瘤特征种族差异是由于地理群体之间的遗传差异造成的。在当地血统和单一变异水平上的进一步研究可能会对疾病结构和肌瘤风险种族差异的遗传机制产生新的见解。