Genome-wide association analyses of gestational phenotypes identify context-specific genetic effects
Abstract
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.
Siyang Liu
PhD in Bioinformatics, Associate Professor, Researcher
Focused on human genomics and bioinformatics research
Hao Zheng
M.Sc in Epidemiology and Health Statistics
Yuqin Gu
PhD in Epidemiology and Health Statistics
Zijing Yang
MPH
Yuandan Wei
MPH
Yanhong Liu
MD, Postdoctoral Researcher
Yanchao Chen
Master student of Public Health
Zijun Wan
PhD student in Epidemiology and Health Statistics
Xinxin Guo
M.Sc. in Epidemiology and Medical Statistics
