Elucidating Shared Genetic Association Between Female Body Mass Index and Preeclampsia

Overview

Journal Commun Biol

Specialty Biology

Date 2025 Feb 26

PMID 40011749

Authors

Fengmei Yang

Zhijian Zha

Fang Gao

Man Wang

Enfu Du

Ziyang Wang

Lei Zhou

Bo Gao

Si Li

Danfeng Zhang

Affiliations

Soon will be listed here.

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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