Elucidating shared genetic association between female body mass index and preeclampsia

Abstract The prevalence of obesity is steadily rising and poses a significant challenge to women’s health. Preeclampsia (PE), a leading cause of maternal and fetal mortality, is significantly linked to a high body mass index (BMI). However, the shared genetic architecture underlying these conditions...

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Bibliographic Details
Main Authors: Fengmei Yang, Zhijian Zha, Fang Gao, Man Wang, Enfu Du, Ziyang Wang, Lei Zhou, Bo Gao, Si Li, Danfeng Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07726-4
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Summary:Abstract The prevalence of obesity is steadily rising and poses a significant challenge to women’s health. Preeclampsia (PE), a leading cause of maternal and fetal mortality, is significantly linked to a high body mass index (BMI). However, the shared genetic architecture underlying these conditions remains poorly understood. In this study, we used summary-level data from large-scale genome-wide association studies of BMI (N = 434,794) and PE (Ncases = 8185; Ncontrols = 234,147) to assess the shared genetic architecture between them. Our findings revealed a significant genetic correlation between BMI and PE, with an estimated sample overlap of approximately 0.8%. We identified roughly 1100 shared genetic variants, with the most notable region of local genetic correlation located in 16q12.2. Enrichment analyses highlighted endothelial dysfunction as a key biological mechanism linking BMI and PE. Additionally, RABEP2 was identified as a novel shared risk gene. Mendelian randomization analysis demonstrated a bidirectional causal relationship between BMI and PE, with blood pressure identified as a key mediator. We identified the shared genetic foundation between BMI and PE, providing valuable insights into the comorbidity of these conditions and offering a new framework for future research into comorbidity.
ISSN:2399-3642