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: 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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author Fengmei Yang
Zhijian Zha
Fang Gao
Man Wang
Enfu Du
Ziyang Wang
Lei Zhou
Bo Gao
Si Li
Danfeng Zhang
author_facet Fengmei Yang
Zhijian Zha
Fang Gao
Man Wang
Enfu Du
Ziyang Wang
Lei Zhou
Bo Gao
Si Li
Danfeng Zhang
author_sort Fengmei Yang
collection DOAJ
description 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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spelling doaj-art-e3b3abdbc8944e6ab9a3b5509ca5531a2025-08-20T03:03:40ZengNature PortfolioCommunications Biology2399-36422025-02-01811910.1038/s42003-025-07726-4Elucidating shared genetic association between female body mass index and preeclampsiaFengmei Yang0Zhijian Zha1Fang Gao2Man Wang3Enfu Du4Ziyang Wang5Lei Zhou6Bo Gao7Si Li8Danfeng Zhang9Taihe Hospital, Hubei University of MedicineCollege of Traditional Chinese Medicine, Hubei University of Chinese MedicineXiangzhou District People’s HospitalTaihe Hospital, Hubei University of MedicineTaihe Hospital, Hubei University of MedicineInstitute of Medicine Nursing, Hubei University of MedicineTaihe Hospital, Hubei University of MedicineTaihe Hospital, Hubei University of MedicineDepartment of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyTaihe Hospital, Hubei University of MedicineAbstract 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.https://doi.org/10.1038/s42003-025-07726-4
spellingShingle Fengmei Yang
Zhijian Zha
Fang Gao
Man Wang
Enfu Du
Ziyang Wang
Lei Zhou
Bo Gao
Si Li
Danfeng Zhang
Elucidating shared genetic association between female body mass index and preeclampsia
Communications Biology
title Elucidating shared genetic association between female body mass index and preeclampsia
title_full Elucidating shared genetic association between female body mass index and preeclampsia
title_fullStr Elucidating shared genetic association between female body mass index and preeclampsia
title_full_unstemmed Elucidating shared genetic association between female body mass index and preeclampsia
title_short Elucidating shared genetic association between female body mass index and preeclampsia
title_sort elucidating shared genetic association between female body mass index and preeclampsia
url https://doi.org/10.1038/s42003-025-07726-4
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