A Dynamic Genetic Atlas of Gestational Phenotypes

The [~]40-week gestational period is central to human reproduction, yet the genetic architecture of diverse gestational phenotypes and their links to maternal late-life health remain unclear. In 111 phenotypes from up to 121,579 Chinese pregnancies (median n = 78,535 per phenotype), we identified 4,688 independent genome-wide significant loci, including 1,703 novel associations. Gestation-specific effects were observed for 7.8% of variants across 30 phenotypes, and 18.7% of signals for 24 longitudinal hematological traits exhibited gene-by-gestational-timing interactions across five antenatal and postpartum periods. Dynamic genetic effects were enriched in growth- and hormone-regulatory pathways, reflecting maternal-fetal interactions. Genetic correlation and Mendelian randomization analyses with 80 diseases and medication traits in Biobank Japan females revealed shared genetic architecture and potential causal links between gestational phenotypes and maternal mid- and late-life health. These results establish a dynamic genetic atlas of human gestational phenotypes with implications for precision maternal-health strategies. Results are visualized at https://monn.pheweb.com/.