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<p>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 <i>n</i> = 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.</p>

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Genome-wide association analyses of gestational phenotypes identify context-specific genetic effects

  • 期刊论文

  • 发表日期：

    2026年7月27日

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  • Siyang Liu,
  • Hao Zheng,
  • Yuqin Gu,
  • Zijing Yang,
  • Jianxin Zhen,
  • Yuandan Wei,
  • Yanhong Liu,
  • Yanchao Chen,
  • Zijun Wan,
  • Xinxin Guo,
  • Liang Hu,
  • Xiaohang Chen,
  • Xiaotian Li,
  • Xiu Qiu,
  • Shujia Huang,
  • Guo-Bo Chen,
  • Zhibin Hu,
  • Shinichi Namba,
  • Masahiro Kanai,
  • Koichi Matsuda,
  • Yukinori Okada,
  • Quanfu Zhang,
  • Fengxiang Wei

摘要

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.