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已发表论文
子痫前期的遗传预测因果风险因素：一项全面的孟德尔随机化研究
Authors Wu H, Sun D, Fang S, Pan Q, Yue C
Received 11 August 2025
Accepted for publication 21 November 2025
Published 3 December 2025 Volume 2025:17 Pages 5105—5116
DOI https://doi.org/10.2147/IJWH.S559901
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Han Wu,1,* Dongmei Sun,2,* Sijia Fang,3 Qiuhui Pan,1,4– 6 Chaoyan Yue3
1Department of Clinical Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Xuyi People’s Hospital, Huai’an, Jiangsu, People’s Republic of China; 3Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai, People’s Republic of China; 5Hainan Branch, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Sanya, Hainan, People’s Republic of China; 6Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chaoyan Yue, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fangxie Road No. 419, Huangpu District, Shanghai, 200011, People’s Republic of China, Email 20111250007@fudan.edu.cn Qiuhui Pan, Department of Clinical Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No. 1678, Pudong New District, Shanghai, 200127, People’s Republic of China, Email panqiuhui_med@163.com
Background: Preeclampsia is a complex hypertensive disorder of pregnancy, significantly impacting maternal and fetal health worldwide. Despite extensive research, its pathogenesis, involving inflammatory, immune, microbiological, and metabolic factors, requires comprehensive elucidation.
Methods: This study applied Mendelian randomization (MR) to investigate causal relationships between multi-omics traits and the risk of preeclampsia. The genome-wide association studies (GWAS) datasets used consisted of immune cells (N = 3757), inflammatory factors (N = 14,824), gut microbiota (N = 7738), circulating metabolites (N 1 = 7824, N 2 = 8299), plasma proteins (N = 3301), and preeclampsia (7212 cases, 194,266 controls). The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses.
Results: Our analysis identified 81 potential causal factors for preeclampsia. Among the most novel and clinically significant findings were several druggable plasma proteins, including Astacin-like metalloendopeptidase (ASTL) and Baculoviral IAP repeat-containing protein 3 (BIRC3), which exhibited strong causal evidence. Furthermore, we identified specific gut microbiota genera, notably Bifidobacterium, as potential protective factors. We also validated the causal roles of key metabolic disturbances, like cysteine and guanidinoacetate, and dysfunctions in specific immune cell populations, particularly regulatory T and B cells.
Conclusion: These findings highlight the intricate interplay of immune, inflammatory, microbiological, metabolic, and protein factors in preeclampsia, suggesting novel diagnostic and therapeutic targets. Further research is warranted to explore these associations in detail.
Keywords: causality, gut microbiome, inflammatory factor, Mendelian randomization, metabolome, multi-omics, preeclampsia
1Department of Clinical Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Xuyi People’s Hospital, Huai’an, Jiangsu, People’s Republic of China; 3Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai, People’s Republic of China; 5Hainan Branch, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Sanya, Hainan, People’s Republic of China; 6Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chaoyan Yue, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fangxie Road No. 419, Huangpu District, Shanghai, 200011, People’s Republic of China, Email 20111250007@fudan.edu.cn Qiuhui Pan, Department of Clinical Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No. 1678, Pudong New District, Shanghai, 200127, People’s Republic of China, Email panqiuhui_med@163.com
Background: Preeclampsia is a complex hypertensive disorder of pregnancy, significantly impacting maternal and fetal health worldwide. Despite extensive research, its pathogenesis, involving inflammatory, immune, microbiological, and metabolic factors, requires comprehensive elucidation.
Methods: This study applied Mendelian randomization (MR) to investigate causal relationships between multi-omics traits and the risk of preeclampsia. The genome-wide association studies (GWAS) datasets used consisted of immune cells (N = 3757), inflammatory factors (N = 14,824), gut microbiota (N = 7738), circulating metabolites (N 1 = 7824, N 2 = 8299), plasma proteins (N = 3301), and preeclampsia (7212 cases, 194,266 controls). The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses.
Results: Our analysis identified 81 potential causal factors for preeclampsia. Among the most novel and clinically significant findings were several druggable plasma proteins, including Astacin-like metalloendopeptidase (ASTL) and Baculoviral IAP repeat-containing protein 3 (BIRC3), which exhibited strong causal evidence. Furthermore, we identified specific gut microbiota genera, notably Bifidobacterium, as potential protective factors. We also validated the causal roles of key metabolic disturbances, like cysteine and guanidinoacetate, and dysfunctions in specific immune cell populations, particularly regulatory T and B cells.
Conclusion: These findings highlight the intricate interplay of immune, inflammatory, microbiological, metabolic, and protein factors in preeclampsia, suggesting novel diagnostic and therapeutic targets. Further research is warranted to explore these associations in detail.
Keywords: causality, gut microbiome, inflammatory factor, Mendelian randomization, metabolome, multi-omics, preeclampsia