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

Thorhildur Olafsdottir; Gudmar Thorleifsson; Patrick Sulem; Olafur A Stefansson; Helga Medek; Karl Olafsson; Orri Ingthorsson; Valur Gudmundsson; Ingileif Jonsdottir; Gisli H Halldorsson; Ragnar P Kristjansson; Michael L Frigge; Lilja Stefansdottir; Jon K Sigurdsson; Asmundur Oddsson; Asgeir Sigurdsson; Hannes P Eggertsson; Pall Melsted; Bjarni V Halldorsson; Sigrun H Lund; Unnur Styrkarsdottir; Valgerdur Steinthorsdottir; Julius Gudmundsson; Hilma Holm; Vinicius Tragante; Folkert W Asselbergs; Unnur Thorsteinsdottir; Daniel F Gudbjartsson; Kristin Jonsdottir; Thorunn Rafnar; Kari Stefansson

doi:10.1038/s42003-020-0857-9

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

Thorhildur Olafsdottir, Gudmar Thorleifsson, Patrick Sulem, Olafur A Stefansson, Helga Medek, Karl Olafsson, Orri Ingthorsson, Valur Gudmundsson, Ingileif Jonsdottir, Gisli H Halldorsson, Ragnar P Kristjansson, Michael L Frigge, Lilja Stefansdottir, Jon K Sigurdsson, Asmundur Oddsson, Asgeir Sigurdsson, Hannes P Eggertsson, Pall Melsted, Bjarni V Halldorsson, Sigrun H LundUnnur Styrkarsdottir, Valgerdur Steinthorsdottir, Julius Gudmundsson, Hilma Holm, Vinicius Tragante, Folkert W Asselbergs, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Kristin Jonsdottir, Thorunn Rafnar, Kari Stefansson

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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.

Original language	English
Article number	129
Pages (from-to)	1-10
Journal	Communications biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-0857-9
Publication status	Published - 1 Dec 2020

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Olafsdottir, T., Thorleifsson, G., Sulem, P., Stefansson, O. A., Medek, H., Olafsson, K., Ingthorsson, O., Gudmundsson, V., Jonsdottir, I., Halldorsson, G. H., Kristjansson, R. P., Frigge, M. L., Stefansdottir, L., Sigurdsson, J. K., Oddsson, A., Sigurdsson, A., Eggertsson, H. P., Melsted, P., Halldorsson, B. V., ... Stefansson, K. (2020). Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank. Communications biology, 3(1), 1-10. Article 129. https://doi.org/10.1038/s42003-020-0857-9

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title = "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 < 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. ",

author = "Thorhildur Olafsdottir and Gudmar Thorleifsson and Patrick Sulem and Stefansson, {Olafur A} and Helga Medek and Karl Olafsson and Orri Ingthorsson and Valur Gudmundsson and Ingileif Jonsdottir and Halldorsson, {Gisli H} and Kristjansson, {Ragnar P} and Frigge, {Michael L} and Lilja Stefansdottir and Sigurdsson, {Jon K} and Asmundur Oddsson and Asgeir Sigurdsson and Eggertsson, {Hannes P} and Pall Melsted and Halldorsson, {Bjarni V} and Lund, {Sigrun H} and Unnur Styrkarsdottir and Valgerdur Steinthorsdottir and Julius Gudmundsson and Hilma Holm and Vinicius Tragante and Asselbergs, {Folkert W} and Unnur Thorsteinsdottir and Gudbjartsson, {Daniel F} and Kristin Jonsdottir and Thorunn Rafnar and Kari Stefansson",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s42003-020-0857-9",

language = "English",

volume = "3",

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Olafsdottir, T, Thorleifsson, G, Sulem, P, Stefansson, OA, Medek, H, Olafsson, K, Ingthorsson, O, Gudmundsson, V, Jonsdottir, I, Halldorsson, GH, Kristjansson, RP, Frigge, ML, Stefansdottir, L, Sigurdsson, JK, Oddsson, A, Sigurdsson, A, Eggertsson, HP, Melsted, P, Halldorsson, BV, Lund, SH, Styrkarsdottir, U, Steinthorsdottir, V, Gudmundsson, J, Holm, H, Tragante, V, Asselbergs, FW, Thorsteinsdottir, U, Gudbjartsson, DF, Jonsdottir, K, Rafnar, T & Stefansson, K 2020, 'Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank', Communications biology, vol. 3, no. 1, 129, pp. 1-10. https://doi.org/10.1038/s42003-020-0857-9

TY - JOUR

T1 - Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank

AU - Olafsdottir, Thorhildur

AU - Thorleifsson, Gudmar

AU - Sulem, Patrick

AU - Stefansson, Olafur A

AU - Medek, Helga

AU - Olafsson, Karl

AU - Ingthorsson, Orri

AU - Gudmundsson, Valur

AU - Jonsdottir, Ingileif

AU - Halldorsson, Gisli H

AU - Kristjansson, Ragnar P

AU - Frigge, Michael L

AU - Stefansdottir, Lilja

AU - Sigurdsson, Jon K

AU - Oddsson, Asmundur

AU - Sigurdsson, Asgeir

AU - Eggertsson, Hannes P

AU - Melsted, Pall

AU - Halldorsson, Bjarni V

AU - Lund, Sigrun H

AU - Styrkarsdottir, Unnur

AU - Steinthorsdottir, Valgerdur

AU - Gudmundsson, Julius

AU - Holm, Hilma

AU - Tragante, Vinicius

AU - Asselbergs, Folkert W

AU - Thorsteinsdottir, Unnur

AU - Gudbjartsson, Daniel F

AU - Jonsdottir, Kristin

AU - Rafnar, Thorunn

AU - Stefansson, Kari

N1 - Funding Information: 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. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85082011163&partnerID=8YFLogxK

U2 - 10.1038/s42003-020-0857-9

DO - 10.1038/s42003-020-0857-9

M3 - Article

C2 - 32184442

SN - 2399-3642

VL - 3

SP - 1

EP - 10

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 129

ER -

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

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