Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank

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 x 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. Thorhildur Olafsdottir et al. report a genome-wide association study of pelvic organ prolapse (POP) in a total of 15,010 cases and 340,734 controls from Iceland and the UK. They identify 8 sequence variants at 7 loci associated with POP that highlight the role of connective tissue metabolism and estrogen in POP.