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Risk Factors for Pelvic Organ Prolapse: Wide-Angled Mendelian Randomization Analysis

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Abstract

Introduction and Hypothesis

We hypothesized that some metabolic factors, lifestyle factors, and socioeconomic factors may have a causal effect on pelvic organ prolapse (POP).

Methods

We selected instruments from corresponding genome-wide association studies (GWAS), which identified independent single nucleotide polymorphisms strongly associated with 12 potential risk factors. Summary statistics for POP were derived from two GWAS datasets, serving for discovery and replication stage. The primary analysis involved the use of the inverse-variance weighting mendelian randomization (MR) method, with additional sensitivity MR analyses conducted.

Results

The univariable mendelian randomization (UVMR) analysis in both the discovery and replication stage provided evidence for significant causal effects between higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI) levels, lower high-density lipoprotein cholesterol (HDL-C) levels, and lower educational attainment and higher POP risk, as well as a suggestive positive causal effect between triglycerides and POP. The multivariable mendelian randomization (MVMR) analysis showed that only HDL-C among the three blood lipid fractions could reduce the risk of POP. Mediation analysis indicated that HDL-C may partially mediate the effect of WHRadjBMI on POP risk, and the causal effect between educational attainment and POP may be mediated through WHRadjBMI and HDL-C.

Conclusions

Our study's evidence supported a causal relationship between WHRadjBMI, triglycerides, HDL-C, educational attainment, and POP risk. This highlights that clinicians may guide the general female population to control obesity and blood lipid levels to reduce the risk of POP.

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Data Availability

Original data generated and analyzed during this study are included in this published article or in the data repositories listed in References. Data that support the findings of this study but are not included in the article or in the online supplementary files are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu City, Sichuan Province, People’s Republic of China

    Zheyu **ong, Mengzhu Yang, Menghua Wang & Zhongyu Jian

  2. Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

    Chi Yuan

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  1. Zheyu **ong
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Contributions

Z.X.: conceptualization, original draft preparation, data collection and analysis; C.Y. and M.Y.: conceptualization, original draft preparation; M.W.: data collection and analysis; Z.J.: resources and supervision.

Corresponding author

Correspondence to Zhongyu Jian.

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Editor in Chief: Maria A. Bortolini

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Zheyu **ong, Chi Yuan, and Mengzhu Yang have contributed equally to this work and share the first authorship.

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**ong, Z., Yuan, C., Yang, M. et al. Risk Factors for Pelvic Organ Prolapse: Wide-Angled Mendelian Randomization Analysis. Int Urogynecol J (2024). https://doi.org/10.1007/s00192-024-05807-2

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