Family history of uterine fibroids significantly modifies associations of GWAS loci with the disease risk: molecular-genetics and bioinformatic analysis

Abstract Uterine fibroids (UF) are among the most common benign tumors in women, yet their genetic underpinnings remain largely unexplored. Given the importance of genetic predisposition and the significance of GWAS-identified loci in UF, we aimed to investigate how family history of UF influences the association between these loci and the disease risk. DNA samples from 241 women with a family history of UF and 947 women without were genotyped for seven GWAS SNPs using probe-based PCR. In patients without a family history of UF, rs547025 SIRT3 was associated with a reduced risk (effect allele C, OR = 0.59, 95 % CI = 0.41–0.83, p = 0.002). Conversely, rs7986407 FOXO1 was linked to an increased risk of UF in those with a family history (effect allele G, OR = 1.94, 95 % CI = 1.03–3.68, p = 0.03). The most significant gene-environment interactions in patients with a family history were observed with pelvic inflammatory disease and GWAS SNPs, while in those without a family history, interactions additionally involved medical abortions. Our bioinformatic analysis uncovered the SNPs’ molecular mechanisms, contributing to UF development.