Department of Endocrinology and Metabolism, The Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110000, P.R. China.
Department of Endocrinology and Metabolism, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang, Heilongjiang, 157011, P.R. China.
J Ovarian Res. 2024 May 7;17(1):95. doi: 10.1186/s13048-024-01420-5.
Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.
We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.
We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.
TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.
Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.
最近的研究揭示了血清维生素 D（VD）水平与多囊卵巢综合征（PCOS）之间的相关性，但因果关系和具体机制仍不确定。
我们旨在探讨血清 VD 与 PCOS 之间的因果关系，以及睾酮在相关病理机制中的作用。
我们使用双向两样本 Mendelian 随机化（TS-MR）分析中的全基因组关联研究（GWAS）数据评估血清 VD 与 PCOS 之间的因果关系。随后，进行 MR 中介分析，以检验睾酮在血清 VD 与 PCOS 之间因果关系中的中介作用。最后，我们整合 GWAS 数据和顺式表达数量性状基因座（cis-eQTLs）数据进行基因注释，并使用潜在相关基因进行功能富集分析，以评估睾酮的参与和潜在机制。
TS-MR 分析表明，血清 VD 水平较低的个体更容易患上 PCOS（OR=0.750，95%CI：0.587-0.959，P=0.022）。MR 中介分析揭示了血清 VD 水平对 PCOS 风险的间接因果作用通过睾酮（OR=0.983，95%CI：0.968-0.998，P=0.025）。功能富集分析表明，一些途径可能参与了 VD-睾酮-PCOS 轴，例如类固醇激素生物合成和自噬过程。
我们的研究结果表明，遗传预测的血清 VD 水平较低可能导致 PCOS 的发病风险增加，这可能是通过增加睾酮的产生介导的。
