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.

妊娠早期出血和产后出血（PPH）具有巨大风险，前者与流产密切相关，后者是孕产妇死亡的首要原因，凸显了对母婴健康的严重影响。我们在荟萃分析中确定了五个与 PPH 相关的基因位点。功能注释分析表明候选基因HAND2 、 TBX3和RAP2C / FRMD7位于三个位点，并显示在每个位点，相关变体位于孕激素受体的结合位点内。与出生体重、妊娠持续时间和子宫肌瘤有很强的遗传相关性。妊娠早期出血没有产生全基因组关联信号，但显示出与各种人类特征的强烈遗传相关性，表明可能存在复杂的多基因病因。我们的结果表明，产后出血与孕激素信号失调有关，而早期出血是一种与潜在健康状况和可能的社会经济状况相关的复杂特征，可能包括尚未确定的遗传因素。