Developing a polygenic risk score for pelvic organ prolapse: a combined risk assessment approach in Chinese women.

Xi CHENG; Lei LI; Xijuan LIN; Na CHEN; Xudong LIU; Yaqian LI; Zhaoai LI; Jian GONG; Qing LIU; Yuling WANG; Juntao WANG; Zhijun XIA; Yongxian LU; Hangmei JIN; Xiaowei ZHANG; Luwen WANG; Juan CHEN; Guorong FAN; Shan DENG; Sen ZHAO; Lan ZHU

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Developing a polygenic risk score for pelvic organ prolapse: a combined risk assessment approach in Chinese women.

Author: Xi CHENG ¹ ; Lei LI ¹ ; Xijuan LIN ¹ ; Na CHEN ¹ ; Xudong LIU ² ; Yaqian LI ³ ; Zhaoai LI ⁴ ; Jian GONG ⁵ ; Qing LIU ⁶ ; Yuling WANG ⁷ ; Juntao WANG ⁸ ; Zhijun XIA ⁹ ; Yongxian LU ¹⁰ ; Hangmei JIN ¹¹ ; Xiaowei ZHANG ¹² ; Luwen WANG ¹³ ; Juan CHEN ¹ ; Guorong FAN ¹ ; Shan DENG ¹ ; Sen ZHAO ¹⁴ ; Lan ZHU ¹⁵
Author Information

1. Department of Obstetrics and Gynecology National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
2. The State Key Laboratory for Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Beijing, 100730, China.
3. Clinical Research Institute, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.
4. Department of Gynecology and Obstetrics, Children's Hospital of Shanxi Province, Taiyuan, 030013, China.
5. Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Wuxi, Wuxi, 214002, China.
6. Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Gansu Province, Lanzhou, 730030, China.
7. Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Foshan, Foshan, 528000, China.
8. Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Guiyang, Guiyang, 550003, China.
9. Department of Gynecology and Obstetrics, Sheng Jing Hospital of China Medical University, Shenyang, 117004, China.
10. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, 100037, China.
11. Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University, Hangzhou, 310006, China.
12. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
13. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
14. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, USA. zhaosen830@gmail.com.
15. Department of Obstetrics and Gynecology National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. zhu_julie@vip.sina.com.
Publication Type:Journal Article
Keywords: genetic risk score; pelvic organ prolapse; risk assessment
MeSH: Humans; Female; Pelvic Organ Prolapse/epidemiology*; Middle Aged; Risk Assessment/methods*; China/epidemiology*; Multifactorial Inheritance; Aged; Risk Factors; Genome-Wide Association Study; Genetic Predisposition to Disease; Case-Control Studies; Adult; Polymorphism, Single Nucleotide; Genetic Risk Score; East Asian People
From: Frontiers of Medicine 2025;19(4):665-674
CountryChina
Language:English
Abstract: Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.