血清维生素D水平与男性不育症之间的关系：一项两样本孟德尔随机化研究

Association between Serum Vitamin D Levels and Male Infertility: A Two-Sample Mendelian Randomization Study

摘要: 目的：由于异质性和混杂因素，维生素D (VD)与男性不育症之间的因果关系尚未达成共识，即使在随机对照试验(RCT)中也是如此。本研究旨在通过孟德尔随机化(MR)探究血清VD (25-OH-D)水平与男性不育症之间的因果关系，并为未来RCT的优化提供补充信息。方法：从GAWS数据库中提取了VD和MFI的单核苷酸多态性(SNP)，进行两样本孟德尔随机化研究，采用逆方差加权法(Inverse Variance Weighted, IVW)、Egger回归法(MR-Egger)、中位数加权法(Weighted Median)等评估VD与MFI之间的因果关联，同时采用异质性检验(Heterogeneity Test)、水平多效性检验(Horizontal pleiotropy Test)、逐个剔除检验(Leave-one-out sensitivity Test)进行敏感性分析，评估MR分析的可靠性和稳定性。结果：共纳入84个与VD密切相关的SNP，遗传预测的VD水平与MFI的风险无关(OR: 0.728, 95% CI: 0.445~1.191; P = 0.207)，这在三种敏感性分析(MR-Egger法，Weighted median法和Weighted mode法)中都是一致的。结论：遗传预测的血清维生素D水平与男性不育症的风险无关，服用VD补充剂可能无法对男性不育症有益。

Abstract: Objective: Due to heterogeneity and confounding factors, there is no consensus on the causal relationship between vitamin D (VD) and male infertility, even in randomized controlled trials (RCTs). This study aims to explore the causal relationship between serum VD (25-OH-D) levels and male infertility through Mendelian randomization (MR) and to provide complementary information for future optimization of RCT. Methods: Single nucleotide polymorphisms (SNP) of VD and MFI were extracted from GAWS database, and two-sample Mendelian randomization study was carried out. Inverse Variance Weighted (IVW), Egger Regression (MR-Egger), Weighted Median (Weighted Median) were used to evaluate the causal association between VD and MFI. Heterogeneity Test, Horizontal pleiotropy Test and Leave-one-out Sensitivity test were used to conduct sensitivity analysis to evaluate the reliability and stability of MR analysis. Results: A total of 84 SNPs closely related to VD were included, and the level of genetically predicted VD was not associated with the risk of MFI (OR: 0.728, 95% CI: 0.445~1.191; P = 0.207), which was consistent with the three sensitivity analyses (MR-Egger, Weighted median and Weighted mode). After excluding SNPs, the conclusion still holds. Conclusion: Genetically predicted serum vitamin D levels are not associated with the risk of male infertility, and taking VD supplements may not be beneficial to male infertility.