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Genome-wide association analyses of gestational phenotypes identify context-specific genetic effects
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DOI：10.1038/s41588-026-02677-w.png)
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Abstract
En 中文
The approximately 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 signals, including 1,703 new associations. Gestation-specific effects were observed for 7.8% of variants across 30 phenotypes; 18.7% of signals for 24 longitudinal hematological traits exhibited genotype-by-gestational-timing interactions across five antenatal and postpartum periods. Dynamic genetic effects were enriched in growth-regulatory 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 overlaps and potential causal links between gestational phenotypes and maternal mid-life and late-life health. These results establish a dynamic genetic atlas of human gestation, providing a framework for precision maternal health. Genome-wide analyses in up to 121,579 pregnant women from China identify genetic associations across 111 phenotypes, including gestation-specific effects and interactions with gestational timing.
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