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 - S Havulinna, Aki
AU - Sole Navais, Pol
AU - Flatley, Christopher
AU - Rye Ostrowski, Sisse
AU - Birger Pedersen, Ole
AU - Erikstrup, Christian
AU - Sørensen, Erik
AU - Mikkelsen, Christina
AU - Topholm Brun, Mie
AU - Aagaard Jensen, Bitten
AU - Brodersen, Thorsten
AU - Ullum, Henrik
AU - FinnGen
AU - Danish Blood Donor Study Genomic Consortium
AU - Estonian Biobank Research Team
AU - Nordic Collaboration for Womens and Reproductive Health
AU - Magnus, Per
AU - A Andreassen, Ole
AU - R Njolstad, Pål
AU - Marie Kolte, Astrid
AU - Krebs, Lone
AU - Nyegaard, Mette
AU - Folkmann Hansen, Thomas
AU - Fenstra, Bjarke
AU - Daly, Mark
AU - M Lindgren, Cecilia
AU - Thorleifsson, Gudmar
AU - A Stefansson, Olafur
AU - Sveinbjornsson, Gardar
AU - F Gudbjartsson, Daniel
AU - Thorsteinsdottir, Unnur
AU - Banasik, Karina
AU - Jacobsson, Bo
AU - Laisk, Triin
AU - Laivuori, Hannele
AU - Stefansson, Kari
AU - Brunak, Søren
AU - Svarre Nielsen, Henriette
PY - 2023/8/15
Y1 - 2023/8/15
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.
KW - genetic and genomic medicine
U2 - 10.1101/2023.08.10.23293932
DO - 10.1101/2023.08.10.23293932
M3 - Preprint
C2 - 37645979
BT - Pregnancy-associated bleeding and genetics
PB - medRxiv
ER -