Abstract：
OBJECTIVE: 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.
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.
摘要：
目的：我们假设一些代谢因素，生活方式因素，和社会经济因素可能对盆腔器官脱垂（POP）有因果关系。
方法：我们从相应的全基因组关联研究（GWAS）中选择了仪器，该研究鉴定出独立的单核苷酸多态性与12个潜在危险因素强相关。POP的汇总统计数据来自两个GWAS数据集，服务于发现和复制阶段。主要分析涉及使用方差逆加权孟德尔随机化（MR）方法，进行了额外的敏感性MR分析。
结果：发现和复制阶段的单变量孟德尔随机化（UVMR）分析提供了证据，证明了根据体重指数（WHRadjBMI）水平调整后的较高腰臀比之间存在显着因果关系。降低高密度脂蛋白胆固醇（HDL-C）水平，较低的教育程度和较高的POP风险，以及甘油三酯和POP之间的积极因果效应。多变量孟德尔随机化（MVMR）分析表明，三种血脂组分中只有HDL-C可以降低POP的风险。中介分析表明，HDL-C可能部分介导WHRadjBMI对POP风险的影响，受教育程度与POP之间的因果关系可能通过WHRadjBMI和HDL-C介导。
结论：我们的研究证据支持WHRadjBMI之间的因果关系，甘油三酯，HDL-C,教育程度,和POP风险。这突出表明，临床医生可以指导一般女性人群控制肥胖和血脂水平，以降低POP的风险。
方法：我们从相应的全基因组关联研究（GWAS）中选择了仪器，该研究鉴定出独立的单核苷酸多态性与12个潜在危险因素强相关。POP的汇总统计数据来自两个GWAS数据集，服务于发现和复制阶段。主要分析涉及使用方差逆加权孟德尔随机化（MR）方法，进行了额外的敏感性MR分析。
结果：发现和复制阶段的单变量孟德尔随机化（UVMR）分析提供了证据，证明了根据体重指数（WHRadjBMI）水平调整后的较高腰臀比之间存在显着因果关系。降低高密度脂蛋白胆固醇（HDL-C）水平，较低的教育程度和较高的POP风险，以及甘油三酯和POP之间的积极因果效应。多变量孟德尔随机化（MVMR）分析表明，三种血脂组分中只有HDL-C可以降低POP的风险。中介分析表明，HDL-C可能部分介导WHRadjBMI对POP风险的影响，受教育程度与POP之间的因果关系可能通过WHRadjBMI和HDL-C介导。
结论：我们的研究证据支持WHRadjBMI之间的因果关系，甘油三酯，HDL-C,教育程度,和POP风险。这突出表明，临床医生可以指导一般女性人群控制肥胖和血脂水平，以降低POP的风险。
