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

• Published in: Communications Biology
• Main Authors: Olafsdottir, Thorhildur, Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Olafur A, Medek, Helga, Olafsson, Karl, Ingthorsson, Orri, Gudmundsson, Valur, Jonsdottir, Ingileif, Halldorsson, Gisli H, Kristjansson, Ragnar P, Frigge, Michael L, Stefansdottir, Lilja, Sigurdsson, Jon K, Oddsson, Asmundur, Sigurdsson, Asgeir, Eggertsson, Hannes P, Melsted, Pall, Halldorsson, Bjarni V, Lund, Sigrun H, Styrkarsdottir, Unnur, Steinthorsdottir, Valgerdur, Gudmundsson, Julius, Holm, Hilma, Tragante, Vinicius, Asselbergs, Folkert W, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F, Jonsdottir, Kristin, Rafnar, Thorunn, Stefansson, Kari
• Other Authors: 1deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. [e-mail]. 2deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. 3Department of Obstetrics and Gynecology, Landspitali University Hospital, 101, Reykjavik, Iceland. 4Department of Obstetrics and Gynecology, Akureyri Hospital, 600, Akureyri, Iceland. 5Faculty of Medicine, School of Health Sciences, University of Iceland, 101, Reykjavik, Iceland. 6Department of Immunology, Landspitali University Hospital, 101, Reykjavik, Iceland. 7School of Engineering and Natural Sciences, University of Iceland, 101, Reykjavik, Iceland. 8School of Science and Engineering, Reykjavik University, 101, Reykjavik, Iceland. 9Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. 10Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK. 11Health Data Research UK and Institute of Health Informatics, University College London, London, UK. 12deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. [e-mail]. 13Faculty of Medicine, School of Health Sciences, University of Iceland, 101, Reykjavik, Iceland. [e-mail].
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2020
• Subjects: Grindarbotn; Genome-Wide Association Study; Pelvic Organ Prolapse; Iceland
• Online Access: http://hdl.handle.net/2336/621369; https://doi.org/10.1038/s42003-020-0857-9

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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. UCL Hospitals NIHR Biomedical Research Centre