The Dynamic Genetic Atlas of 122 Gestational Phenotypes

The gestational period, spanning approximately 40 weeks from fertilization to birth, is fundamental to human reproduction. Health monitoring during this period involves systematic prenatal and postpartum examinations, guided by indicators collectively termed gestational phenotypes under the national medical insurance framework. Despite their clinical importance, the genetic basis of these phenotypes and their links to later-life health outcomes remain poorly understood. In this large-scale genetic study, we analyzed 122 gestational phenotypes in 121,579 Chinese pregnancies, encompassing anthropometric metrics, blood biomarkers, and common gestational complications and outcomes. We identified 3,845 genetic loci, including 1,893 novel loci, and uncovered gestation-specific genetic effects in 23 phenotypes, with proportions ranging from 0% to 100%. These loci were enriched in pathways related to hormonal regulation, cell growth and immune function. Longitudinal genome-wide association analyses of repeated measures across 24 complete blood cell phenotypes revealed significant gene-by-gestational timing interactions for 17.8% of loci across five gestational and postpartum periods. Mendelian Randomization of 220 mid- and late-life phenotypes identified 73 causal associations between gestational phenotypes and chronic diseases risks. These findings provide critical insights into the genetic architecture of human gestational phenotypes and their implications for long-term health, providing a foundation for advancing population health during gestation. Visualization of results is available at https://monn.pheweb.com/.