Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage

Research output: Working paper › Preprint › Research

Standard

Pregnancy-Associated Bleeding and Genetics : Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage. / Westergaard, David; Steinthorsdottir, Valgerdur; Stefansdottir, Lilja; Rohde, Palle Duun; Wu, Xiaoping; Geller, Frank; Tyrmi, Jaakko; Havulinna, Aki S; Navais, Pol Sole; Flatley, Christopher; Ostrowski, Sisse Rye; Pedersen, Ole Birger; Erikstrup, Christian; Sørensen, Erik; Mikkelsen, Christina; Brun, Mie Topholm; Jensen, Bitten Aagaard; Brodersen, Thorsten; Ullum, Henrik; Magnus, Per; Andreassen, Ole A; Njolstad, Pål R; Krebs, Lone; Hansen, Thomas Folkmann; Banasik, Karina; Brunak, Søren; Nielsen, Henriette Svarre; FinnGen.

medRxiv, 2023.

Research output: Working paper › Preprint › Research

Harvard

Westergaard, D, Steinthorsdottir, V, Stefansdottir, L, Rohde, PD, Wu, X, Geller, F, Tyrmi, J, Havulinna, AS, Navais, PS, Flatley, C, Ostrowski, SR, Pedersen, OB, Erikstrup, C, Sørensen, E, Mikkelsen, C, Brun, MT, Jensen, BA, Brodersen, T, Ullum, H, Magnus, P, Andreassen, OA, Njolstad, PR, Krebs, L, Hansen, TF, Banasik, K, Brunak, S, Nielsen, HS & FinnGen 2023 'Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage' medRxiv. https://doi.org/10.1101/2023.08.10.23293932

APA

Westergaard, D., Steinthorsdottir, V., Stefansdottir, L., Rohde, P. D., Wu, X., Geller, F., Tyrmi, J., Havulinna, A. S., Navais, P. S., Flatley, C., Ostrowski, S. R., Pedersen, O. B., Erikstrup, C., Sørensen, E., Mikkelsen, C., Brun, M. T., Jensen, B. A., Brodersen, T., Ullum, H., ... FinnGen (2023). Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage. medRxiv. medRxiv https://doi.org/10.1101/2023.08.10.23293932

Vancouver

Westergaard D, Steinthorsdottir V, Stefansdottir L, Rohde PD, Wu X, Geller F et al. Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage. medRxiv. 2023. https://doi.org/10.1101/2023.08.10.23293932

Author

Westergaard, David ; Steinthorsdottir, Valgerdur ; Stefansdottir, Lilja ; Rohde, Palle Duun ; Wu, Xiaoping ; Geller, Frank ; Tyrmi, Jaakko ; Havulinna, Aki S ; Navais, Pol Sole ; Flatley, Christopher ; Ostrowski, Sisse Rye ; Pedersen, Ole Birger ; Erikstrup, Christian ; Sørensen, Erik ; Mikkelsen, Christina ; Brun, Mie Topholm ; Jensen, Bitten Aagaard ; Brodersen, Thorsten ; Ullum, Henrik ; Magnus, Per ; Andreassen, Ole A ; Njolstad, Pål R ; Krebs, Lone ; Hansen, Thomas Folkmann ; Banasik, Karina ; Brunak, Søren ; Nielsen, Henriette Svarre ; FinnGen. / Pregnancy-Associated Bleeding and Genetics : Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage. medRxiv, 2023. (medRxiv).

Bibtex

@techreport{8287651ce7ab43f7b736e8e59077c535,
title = "Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage",
abstract = "Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, HAND2, TBX3, and RAP2C/ FRMD7, at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status. ",
author = "David Westergaard and Valgerdur Steinthorsdottir and Lilja Stefansdottir and Rohde, {Palle Duun} and Xiaoping Wu and Frank Geller and Jaakko Tyrmi and Havulinna, {Aki S} and Navais, {Pol Sole} and Christopher Flatley and Ostrowski, {Sisse Rye} and Pedersen, {Ole Birger} and Christian Erikstrup and Erik S{\o}rensen and Christina Mikkelsen and Brun, {Mie Topholm} and Jensen, {Bitten Aagaard} and Thorsten Brodersen and Henrik Ullum and Per Magnus and Andreassen, {Ole A} and Njolstad, {P{\aa}l R} and Lone Krebs and Hansen, {Thomas Folkmann} and Karina Banasik and S{\o}ren Brunak and Nielsen, {Henriette Svarre} and FinnGen",
year = "2023",
doi = "10.1101/2023.08.10.23293932",
language = "English",
series = "medRxiv",
publisher = "medRxiv",
type = "WorkingPaper",
institution = "medRxiv",

}

RIS

TY - UNPB

T1 - Pregnancy-Associated Bleeding and Genetics

T2 - Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage

AU - Westergaard, David

AU - Steinthorsdottir, Valgerdur

AU - Stefansdottir, Lilja

AU - Rohde, Palle Duun

AU - Wu, Xiaoping

AU - Geller, Frank

AU - Tyrmi, Jaakko

AU - Havulinna, Aki S

AU - Navais, Pol Sole

AU - Flatley, Christopher

AU - Ostrowski, Sisse Rye

AU - Pedersen, Ole Birger

AU - Erikstrup, Christian

AU - Sørensen, Erik

AU - Mikkelsen, Christina

AU - Brun, Mie Topholm

AU - Jensen, Bitten Aagaard

AU - Brodersen, Thorsten

AU - Ullum, Henrik

AU - Magnus, Per

AU - Andreassen, Ole A

AU - Njolstad, Pål R

AU - Krebs, Lone

AU - Hansen, Thomas Folkmann

AU - Banasik, Karina

AU - Brunak, Søren

AU - Nielsen, Henriette Svarre

AU - FinnGen

PY - 2023

Y1 - 2023

N2 - Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, HAND2, TBX3, and RAP2C/ FRMD7, at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status.

AB - Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, HAND2, TBX3, and RAP2C/ FRMD7, at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status.

U2 - 10.1101/2023.08.10.23293932

DO - 10.1101/2023.08.10.23293932

M3 - Preprint

C2 - 37645979

T3 - medRxiv

BT - Pregnancy-Associated Bleeding and Genetics

PB - medRxiv

ER -

ID: 380417232