Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China.
Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Sci Rep. 2024 Oct 13;14(1):23931. doi: 10.1038/s41598-024-75816-0.
Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants within joint genomic loci shared between PCOS and T-related traits. Functional annotations suggested that these variants might impact PCOS by modulating nearby genes, such as FSHB. Our findings support the hypothesis that PCOS is significantly influenced by androgen abnormalities. Additionally, this study identified several causal variants potentially involved in shared biological mechanisms between PCOS and T regulation.
睾酮（T）是多囊卵巢综合征（PCOS）的关键预测因子，但 T 和 PCOS 之间的遗传重叠尚未确定。在这里，我们利用来自大规模全基因组关联研究的遗传数据集，使用连锁不平衡评分回归和双变量因果混合模型方法评估了 PCOS 与三种 T 相关特征之间的遗传相关性和多基因重叠。联合虚假发现率（conjFDR）方法用于识别共享的因果变异。使用 FUMA 对变异进行功能注释。总 T 和生物可利用 T 与 PCOS 呈正相关，而性激素结合球蛋白（SHBG）呈负相关。所有三种特征与 PCOS 均表现出广泛的遗传重叠，至少有 68%的 T 相关变异影响 PCOS。conjFDR 揭示了 PCOS 和 T 相关特征之间共同基因组位点内的 4 到 6 个因果变异。功能注释表明，这些变异可能通过调节附近的基因，如 FSHB，来影响 PCOS。我们的研究结果支持这样一种假设，即 PCOS 受到雄激素异常的显著影响。此外，本研究还鉴定了一些潜在涉及 PCOS 和 T 调节之间共享生物学机制的因果变异。
