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.