Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage

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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 severe impact on maternal-fetal health. We identified five genetic loci linked to PPH in a meta-analysis. 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. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.

Original languageEnglish
JournalNature Genetics
Volume56
Issue number8
Pages (from-to)1597-1603
Number of pages7
ISSN1061-4036
DOIs
Publication statusPublished - 2024

Bibliographical note

© 2024. The Author(s).

    Research areas

  • Humans, Female, Genome-Wide Association Study, Postpartum Hemorrhage/genetics, Pregnancy, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genetic Loci, Receptors, Progesterone/genetics

ID: 403619117