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

Abstract 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 dia...

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Bibliographic Details
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
Format: Article in Journal/Newspaper
Language:English
Published: Springer Science and Business Media LLC 2020
Subjects:
General Agricultural and Biological Sciences
General Biochemistry, Genetics and Molecular Biology
Medicine (miscellaneous)
Iceland
Online Access:http://dx.doi.org/10.1038/s42003-020-0857-9
http://www.nature.com/articles/s42003-020-0857-9.pdf
http://www.nature.com/articles/s42003-020-0857-9
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Summary:Abstract 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.

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