Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10⁻⁸); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.

盆腔器官脱垂（POP）是一个或多个盆腔器官向下下降，导致阴道壁和/或子宫突出。我们利用冰岛和英国生物银行的数据进行了 POP 的全基因组关联研究，共有 15,010 例医院诊断代码病例和 340,734 名女性对照，发现 7 个位点的 8 个序列变异与 POP 相关（ P <  5 × 10 ^-8 ); 七种常见（次要等位基因频率 > 5%），一种次要等位基因频率为 4.87%。一些与 POP 相关的变异也与类似的病理生理学特征相关。其中，rs3820282可能改变WNT4的雌激素调节，也与子宫肌瘤、妊娠持续时间和子宫内膜异位症相关。EFEMP1的 Rs3791675是一种参与结缔组织稳态的基因，也与疝气和腕管综合症有关。我们的结果强调了结缔组织代谢和雌激素暴露在 POP 病因中的作用。