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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1453277
This article is part of the Research Topic Hypertension in Obese Women: Gender-Specific Challenges and Solutions View all 4 articles

Causal Pathways in Preeclampsia: A Multidimensional Mendelian Randomization Study in European Populations

Provisionally accepted
Zilong Tan Zilong Tan 1Mengdi Ding Mengdi Ding 1Jianwu Shen Jianwu Shen 1,2Yuxiao Huang Yuxiao Huang 1Junru Li Junru Li 2Aochuan Sun Aochuan Sun 1Jing Hong Jing Hong 3Yan Yang Yan Yang 4Sheng He Sheng He 5Pei Chao Pei Chao 6Ran Luo Ran Luo 1*
  • 1 Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
  • 2 Qinghai Hospital of Traditional Chinese Medicine, Xining, Qinghai Province, China
  • 3 Key Laboratory of Carcinogenesis and Translational Research, Beijing Cancer Hospital, Peking University, Beijing, Beijing Municipality, China
  • 4 Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
  • 5 First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China
  • 6 China Academy of Traditional Chinese Medicine Hospital of Ophthalmology, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Abstracts Purpose: Our study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality. Methods: Employing the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran’s Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification. Results: Our analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses. Conclusion: This extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

    Keywords: Preeclampsia, Mendelian randomization, genetic determinants, causal associations, metabolic disorders, Immune and Inflammatory Factors, Serum uric acid levels

    Received: 22 Jun 2024; Accepted: 15 Aug 2024.

    Copyright: © 2024 Tan, Ding, Shen, Huang, Li, Sun, Hong, Yang, He, Chao and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ran Luo, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.