PDF(Pubmed)
Abstract：
Recurrent pregnancy loss is a distressing event during pregnancy, and understanding its causal factors is crucial. Follistatin, a glycoprotein involved in folliculogenesis and embryogenesis, has been implicated as a potential contributor to the risk of spontaneous abortion. However, establishing a causal relationship requires rigorous investigation using robust methods.
In this study, we utilized mendelian randomization (MR), a powerful genetic epidemiological approach, to examine the causal relationship between follistatin levels and spontaneous abortion. We obtained instrumental variables strongly associated with follistatin levels from large-scale genome-wide association from the IEU database. The inverse variance weighting (IVW) method was taken as gold standard. We also performed sensitivity test to evaluate the robustness of our result.
MR analysis revealed a significant causal relationship between low follistatin levels and spontaneous abortion (p = 0.03). Sensitivity analyses, including pleiotropy test, heterogeneity test, and leave-one-out analysis, all supported the robustness of our findings.
Our study provides compelling evidence supporting the causal relationship between low follistatin levels and increased risk of spontaneous abortion. These findings underscore the importance of follistatin in the etiology of spontaneous abortion and suggest potential preventive interventions. Modulating follistatin levels or relevant pathways could hold promise for reducing the incidence of spontaneous abortion and improving reproductive outcomes. The utilization of MRs strengthens the validity of our results by mitigating confounding and reverse causality biases. Further research is needed to elucidate the underlying molecular mechanisms and explore therapeutic strategies targeting follistatin levels.
In this study, we utilized mendelian randomization (MR), a powerful genetic epidemiological approach, to examine the causal relationship between follistatin levels and spontaneous abortion. We obtained instrumental variables strongly associated with follistatin levels from large-scale genome-wide association from the IEU database. The inverse variance weighting (IVW) method was taken as gold standard. We also performed sensitivity test to evaluate the robustness of our result.
MR analysis revealed a significant causal relationship between low follistatin levels and spontaneous abortion (p = 0.03). Sensitivity analyses, including pleiotropy test, heterogeneity test, and leave-one-out analysis, all supported the robustness of our findings.
Our study provides compelling evidence supporting the causal relationship between low follistatin levels and increased risk of spontaneous abortion. These findings underscore the importance of follistatin in the etiology of spontaneous abortion and suggest potential preventive interventions. Modulating follistatin levels or relevant pathways could hold promise for reducing the incidence of spontaneous abortion and improving reproductive outcomes. The utilization of MRs strengthens the validity of our results by mitigating confounding and reverse causality biases. Further research is needed to elucidate the underlying molecular mechanisms and explore therapeutic strategies targeting follistatin levels.
摘要：
■反复妊娠失败是怀孕期间的一个令人痛苦的事件，了解其因果因素至关重要。Follistatin,一种参与卵泡发育和胚胎发育的糖蛋白，被认为是导致自然流产风险的潜在因素。然而,建立因果关系需要使用稳健的方法进行严格的调查。
■在这项研究中，我们利用孟德尔随机化(MR)，一种强大的遗传流行病学方法，探讨卵泡抑素水平与自然流产之间的因果关系。我们从IEU数据库的大规模全基因组关联中获得了与卵泡抑素水平密切相关的工具变量。以方差逆加权(IVW)方法作为金标准。我们还进行了敏感性测试，以评估我们结果的稳健性。
■MR分析显示，低卵泡抑素水平与自然流产之间存在显着因果关系（p=0.03）。敏感性分析，包括多效性测试，异质性检验，和遗漏分析，所有人都支持我们研究结果的稳健性.
我们的研究提供了令人信服的证据支持低卵泡抑素水平与自然流产风险增加之间的因果关系。这些发现强调了卵泡抑素在自然流产病因中的重要性，并建议了潜在的预防性干预措施。调节卵泡抑素水平或相关途径可能有望降低自然流产的发生率并改善生殖结局。MR的利用通过减轻混杂和反向因果关系偏差来增强我们结果的有效性。需要进一步的研究来阐明潜在的分子机制并探索针对卵泡抑素水平的治疗策略。
■在这项研究中，我们利用孟德尔随机化(MR)，一种强大的遗传流行病学方法，探讨卵泡抑素水平与自然流产之间的因果关系。我们从IEU数据库的大规模全基因组关联中获得了与卵泡抑素水平密切相关的工具变量。以方差逆加权(IVW)方法作为金标准。我们还进行了敏感性测试，以评估我们结果的稳健性。
■MR分析显示，低卵泡抑素水平与自然流产之间存在显着因果关系（p=0.03）。敏感性分析，包括多效性测试，异质性检验，和遗漏分析，所有人都支持我们研究结果的稳健性.
我们的研究提供了令人信服的证据支持低卵泡抑素水平与自然流产风险增加之间的因果关系。这些发现强调了卵泡抑素在自然流产病因中的重要性，并建议了潜在的预防性干预措施。调节卵泡抑素水平或相关途径可能有望降低自然流产的发生率并改善生殖结局。MR的利用通过减轻混杂和反向因果关系偏差来增强我们结果的有效性。需要进一步的研究来阐明潜在的分子机制并探索针对卵泡抑素水平的治疗策略。
