The Dynamic Genetic Atlas of 122 Gestational Phenotypes

The gestational period, spanning approximately 40 weeks from fertilization to birth, is pivotal in human reproduction. Monitoring the health of pregnant women and newborns during this period involves systematic prenatal and postpartum examinations, guided by indicators established under the national medical insurance system, collectively termed gestational phenotypes. However, our understanding of the genetic basis of these phenotypes and their intricate relationship with maternal long-term health outcomes remain markedly limited. We conducted comprehensive genetic investigations into 122 gestational phenotypes among 121,579 Chinese pregnancies. These phenotypes included anthropometric metrics, comprehensive blood biomarker measurements, and common gestational complications and outcomes. We identified 3,845 genetic loci, 1,385 of which are novel. Our analyses revealed gestation-specific genetic effects, ranging from proportion 0% to 100% for 23 phenotypes, highlighting genes and pathways predominantly enriched in response to hormones, growth and immune function. Longitudinal trajectory genome-wide association study (GWAS) analyses of repeated measures across 24 complete blood cell phenotypes revealed that 17.8% of the genetic variants exhibited significant interactions with gestational timing across five gestational and postpartum periods. Two-sample univariable and multivariable Mendelian Randomization (MR) analyses of 220 mid- and old-age phenotypes suggested causal associations between gestational phenotypes and the risk of chronic diseases in later life. These findings provide initial insights into the genetic foundations of human gestational phenotypes and their relationship with long-term health, laying a basis for advanced population health during gestation.