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

• Published in: Communications Biology
• Main Authors: Ólafsdóttir, Thorhildur, Thorleifsson, Gudmar, sulem, patrick, Stefánsson, Ólafur A., Medek, Helga, Olafsson, Karl, Ingþórsson, Orri, Guðmundsson, Valur, Jonsdottir, Ingileif, Halldorsson, Gisli, Kristjansson, Ragnar, Frigge, Michael L., Stefánsdóttir, Lilja, Sigurðsson, Jón K., Oddsson, Asmundur, Sigurðsson, Ásgeir, Eggertsson, Hannes P., Melsted, Páll, Halldórsson, Bjarni, Lund, Sigrún Helga, Styrkarsdottir, Unnur, Steinthorsdottir, Valgerdur, Gudmundsson, Julius, Holm, Hilma, Tragante do O, Vinicius, Asselbergs, Folkert, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel, Jónsdóttir, Kristín, Rafnar, Thorunn, Stefansson, Kari
• Other Authors: Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræðideild (HR), Department of Engineering (RU), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Tæknisvið (HR), School of Technology (RU), Háskóli Íslands, University of Iceland, Háskólinn í Reykjavík, Reykjavik University
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Science and Business Media LLC 2020
• Subjects: Genome-wide association; Pelvic organ prolapse; Uterus; Pathophysiology; Genes; Erfðarannsóknir; Leg; Grindargliðnun; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/2359; https://doi.org/10.1038/s42003-020-0857-9

Publisher's version (útgefin grein) 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. This research has been conducted using the UK Biobank Resource under Application Number 24898 and 24711. We thank the individuals who participated in the study and whose contribution made this work possible. Folkert Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. Peer Reviewed