A large-scale genome-wide association study on female genital tract polyps highlights role of DNA repair, cell proliferation, and cell growth.

This article presents the first large-scale genome-wide association study (GWAS) meta-analysis investigating the genetic risk loci associated with female genital tract (FGT) polyps, primarily endometrial polyps (EPs). Analyzing data from 36,984 women with FGT polyps and 420,993 controls of European ancestry across three biobanks, the study identified 16 significant genomic risk loci implicating genes involved in DNA repair, cell proliferation, and growth, some of which overlap with loci previously linked to endometrial cancer and uterine fibroids. Genetic correlation analyses revealed positive associations with body mass index, reproductive traits, and uterine fibroids, and negative correlations with menopause and sex hormone-binding globulin levels, suggesting shared biological mechanisms between benign polyp development and cancerous processes. Phenome-wide association analyses further showed increased prevalence of endometriosis, irregular menstruation, and various benign and malignant neoplasms among women with FGT polyps. These findings enhance understanding of the genetic architecture of FGT polyps and may inform future diagnostic and therapeutic strategies.