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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 diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P?-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.

SUBMITTER: Olafsdottir T

PROVIDER: S-EPMC7078216 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Olafsdottir Thorhildur T Thorleifsson Gudmar G Sulem Patrick P Stefansson Olafur A OA Medek Helga H Olafsson Karl K Ingthorsson Orri O Gudmundsson Valur V Jonsdottir Ingileif I Halldorsson Gisli H GH Kristjansson Ragnar P RP Frigge Michael L ML Stefansdottir Lilja L Sigurdsson Jon K JK Oddsson Asmundur A Sigurdsson Asgeir A Eggertsson Hannes P HP Melsted Pall P Halldorsson Bjarni V BV Lund Sigrun H SH Styrkarsdottir Unnur U Steinthorsdottir Valgerdur V Gudmundsson Julius J Holm Hilma H Tragante Vinicius V Asselbergs Folkert W FW Thorsteinsdottir Unnur U Gudbjartsson Daniel F DF Jonsdottir Kristin K Rafnar Thorunn T Stefansson Kari K

Communications biology 20200317 1

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<sup>-8</sup>); seven common (minor allele frequency >5%) and one with minor allele freq ...[more]

PMID: 32184442

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Project description:BackgroundPrevious studies on physical activity (PA) and pelvic organ prolapse (POP) were largely limited to self-reported PA in athletes, soldiers, and women in postpartum. We aimed to investigate the association of accelerometer-measured PA and sedentary behavior with the risk of POP in middle-aged and elderly women.MethodsIn this prospective cohort derived from the UK Biobank, the intensity and duration of PA and sedentary behavior were measured with wrist-worn accelerometers over a 7-day period in 2013-2015 for 47,674 participants (aged 42.8-77.9 years) without pre-existing POP. Participants were followed up until the end of 2022, during which incident POP was ascertained mainly by the electronic health records. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to assess the associations of interest. Isotemporal substitution models were applied to test the effects of substituting a type of activity with equivalent duration of others.ResultsDuring a median follow-up of 8.0 years, 779 cases of POP were recorded. The duration of light-intensity PA (LPA) was positively whereas sedentary time was negatively associated with the risk of POP. Every additional 1 h/day of LPA elevated the risk of POP by 18% (95% confidence interval [CI], 10%-26%). In contrast, the risk decreased by 5% (95% CI, 0-8%) per 1 h/day increment in sedentary behavior. No associations were found between moderate-intensity PA (MPA) or vigorous-intensity PA (VPA) and POP, except that women who had a history of hysterectomy were more likely to develop POP when performing more VPA (53% higher risk for every additional 15 min/day). Substituting 1 h/day of LPA with equivalent sedentary time was associated with a 18% (95% CI, 11%-24%) lower risk of POP. The risk can also be reduced by 17% (95% CI, 7%-25%) through substituting 30 min/day of LPA with MPA.ConclusionsMore time spent in LPA or less sedentary time was linked to an elevated risk of POP in middle-aged and elderly women, while MPA or VPA was not. Substituting LPA with equivalent duration of sedentary behavior or MPA may lower the risk of POP.

Dataset Information

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

Publications

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

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