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

Thorhildur Ólafsdóttir; Gudmar Thorleifsson; patrick sulem; Ólafur A. Stefánsson; Helga Medek; Karl Olafsson; Orri Ingþórsson; Valur Guðmundsson; Ingileif Jonsdottir; Gisli Halldorsson; Ragnar Kristjansson; Michael L. Frigge; Lilja Stefánsdóttir; Jón K. Sigurðsson; Asmundur Oddsson; Ásgeir Sigurðsson; Hannes P. Eggertsson; Páll Melsted; Bjarni Halldórsson; Sigrún Helga Lund; Unnur Styrkarsdottir; Valgerdur Steinthorsdottir; Julius Gudmundsson; Hilma Holm; Vinicius Tragante do O; Folkert Asselbergs; Unnur Thorsteinsdottir; Daniel Gudbjartsson; Kristín Jónsdóttir; 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 Ólafsdóttir
, Gudmar Thorleifsson
, patrick sulem
, Ólafur A. Stefánsson
, Helga Medek
, Karl Olafsson
, Orri Ingþórsson
, Valur Guðmundsson
, Ingileif Jonsdottir
, Gisli Halldorsson
, Ragnar Kristjansson
, Michael L. Frigge
, Lilja Stefánsdóttir
, Jón K. Sigurðsson
, Asmundur Oddsson
, Ásgeir Sigurðsson
, Hannes P. Eggertsson
, Páll Melsted
, Bjarni Halldórsson
, Sigrún Helga Lund

Unnur Styrkarsdottir, Valgerdur Steinthorsdottir, Julius Gudmundsson, Hilma Holm, Vinicius Tragante do O, Folkert Asselbergs, Unnur Thorsteinsdottir, Daniel Gudbjartsson, Kristín Jónsdóttir, Thorunn Rafnar, Kari Stefansson

University of Iceland, Reykjavik University, Landspitali

Research output: Contribution to journal › Article › peer-review

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
Pages (from-to)	129
Number of pages	129
Journal	Communications Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-0857-9
Publication status	Published - 17 Mar 2020

Other keywords

Erfðarannsóknir
Genes
Genome-Wide Association Study
Genome-wide association
Grindarbotn
Grindargliðnun
Leg
Pathophysiology
Pelvic organ prolapse
Uterus

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10.1038/s42003-020-0857-9

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Ólafsdóttir, T., Thorleifsson, G., sulem, P., Stefánsson, Ó. A., Medek, H., Olafsson, K., Ingþórsson, O., Guðmundsson, V., Jonsdottir, I., Halldorsson, G., Kristjansson, R., Frigge, M. L., Stefánsdóttir, L., Sigurðsson, J. K., Oddsson, A., Sigurðsson, Á., Eggertsson, H. P., Melsted, P., Halldórsson, B., ... Stefansson, K. (2020). Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank. Communications Biology, 3(1), 129. https://doi.org/10.1038/s42003-020-0857-9

@article{398b009ff0e243a1b39d8385f713e1c3,

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.",

keywords = "Erf{\dh}aranns{\'o}knir, Genes, Genome-Wide Association Study, Genome-wide association, Grindarbotn, Grindargli{\dh}nun, Leg, Pathophysiology, Pelvic organ prolapse, Uterus, Erf{\dh}aranns{\'o}knir, Genes, Genome-Wide Association Study, Genome-wide association, Grindarbotn, Grindargli{\dh}nun, Leg, Pathophysiology, Pelvic organ prolapse, Uterus",

author = "Thorhildur {\'O}lafsd{\'o}ttir and Gudmar Thorleifsson and patrick sulem and Stef{\'a}nsson, \{{\'O}lafur A.\} and Helga Medek and Karl Olafsson and Orri Ing{\th}{\'o}rsson and Valur Gu{\dh}mundsson and Ingileif Jonsdottir and Gisli Halldorsson and Ragnar Kristjansson and Frigge, \{Michael L.\} and Lilja Stef{\'a}nsd{\'o}ttir and Sigur{\dh}sson, \{J{\'o}n K.\} and Asmundur Oddsson and {\'A}sgeir Sigur{\dh}sson and Eggertsson, \{Hannes P.\} and P{\'a}ll Melsted and Bjarni Halld{\'o}rsson and Lund, \{Sigr{\'u}n Helga\} and Unnur Styrkarsdottir and Valgerdur Steinthorsdottir and Julius Gudmundsson and Hilma Holm and \{Tragante do O\}, Vinicius and Folkert Asselbergs and Unnur Thorsteinsdottir and Daniel Gudbjartsson and Krist{\'i}n J{\'o}nsd{\'o}ttir and Thorunn Rafnar and Kari Stefansson",

year = "2020",

month = mar,

day = "17",

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

language = "English",

volume = "3",

pages = "129",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Ólafsdóttir, T, Thorleifsson, G, sulem, P, Stefánsson, ÓA, Medek, H, Olafsson, K, Ingþórsson, O, Guðmundsson, V, Jonsdottir, I, Halldorsson, G, Kristjansson, R, Frigge, ML, Stefánsdóttir, L, Sigurðsson, JK, Oddsson, A, Sigurðsson, Á, Eggertsson, HP, Melsted, P, Halldórsson, B, Lund, SH, Styrkarsdottir, U, Steinthorsdottir, V, Gudmundsson, J, Holm, H, Tragante do O, V, Asselbergs, F, Thorsteinsdottir, U, Gudbjartsson, D, Jónsdóttir, 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, pp. 129. 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 - Ólafsdóttir, Thorhildur

AU - Thorleifsson, Gudmar

AU - sulem, patrick

AU - Stefánsson, Ólafur A.

AU - Medek, Helga

AU - Olafsson, Karl

AU - Ingþórsson, Orri

AU - Guðmundsson, Valur

AU - Jonsdottir, Ingileif

AU - Halldorsson, Gisli

AU - Kristjansson, Ragnar

AU - Frigge, Michael L.

AU - Stefánsdóttir, Lilja

AU - Sigurðsson, Jón K.

AU - Oddsson, Asmundur

AU - Sigurðsson, Ásgeir

AU - Eggertsson, Hannes P.

AU - Melsted, Páll

AU - Halldórsson, Bjarni

AU - Lund, Sigrún Helga

AU - Styrkarsdottir, Unnur

AU - Steinthorsdottir, Valgerdur

AU - Gudmundsson, Julius

AU - Holm, Hilma

AU - Tragante do O, Vinicius

AU - Asselbergs, Folkert

AU - Thorsteinsdottir, Unnur

AU - Gudbjartsson, Daniel

AU - Jónsdóttir, Kristín

AU - Rafnar, Thorunn

AU - Stefansson, Kari

PY - 2020/3/17

Y1 - 2020/3/17

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.

KW - Erfðarannsóknir

KW - Genes

KW - Genome-Wide Association Study

KW - Genome-wide association

KW - Grindarbotn

KW - Grindargliðnun

KW - Leg

KW - Pathophysiology

KW - Pelvic organ prolapse

KW - Uterus

KW - Erfðarannsóknir

KW - Genes

KW - Genome-Wide Association Study

KW - Genome-wide association

KW - Grindarbotn

KW - Grindargliðnun

KW - Leg

KW - Pathophysiology

KW - Pelvic organ prolapse

KW - Uterus

U2 - 10.1038/s42003-020-0857-9

DO - 10.1038/s42003-020-0857-9

M3 - Article

C2 - 32184442

SN - 2399-3642

VL - 3

SP - 129

JO - Communications Biology

JF - Communications Biology

IS - 1

ER -

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

Abstract

Other keywords

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