Significant interpopulation differentiation at candidate loci may underlie ethnic disparities in the prevalence of uterine fibroids

Abstract

Uterine fibroids (UF) are a significant health problem bearing a substantial economic burden. The prevalence of the disease is disparate in populations of different ethnic ancestry being the highest in Africans. This study analysed worldwide population differentiation at the genomewide association study (GWAS)-significant UF-associated loci to test a hypothesis that population structure at risk loci might underlie the observed interethnic disparities in the prevalence. In total, 28 single-nucleotide polymorphism (SNP) with the GWAS significance for European Caucasians were analysed in female cohorts of the European, admixed American, African, east Asian, and South Asian populations retrieved from the 1000 Genomes Project data. Common population genetic structure estimators, polygenic risk score (unweighted and weighted) were computed. According to the Fisher's exact test, the populations were significantly differentiated (P<< 10-5) at the UF risk loci. The polygenic risk scores did not differ significantly when calculated across all loci. However, they differed when only loci with risk alleles showing the enrichment/depletion patterns correlating with the documented ethnicity-specific risk of the disease were included in the calculation. The population genetic structure at the UF risk loci is apparently a significant factor underlying the observed between-ethnic disparities in the disease prevalence.