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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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
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| 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. |
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| ISSN: | 2399-3642 |