INTRODUCTION Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS WWE registered at West China Hospital between January 2021 and October 2021 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded and blood samples were collected for hormones, glucose metabolism testing and whole-genome sequencing. RESULTS After sample sequencing, quality control and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS 'burden score' of each individual were calculated to count the deleterious variants. A total of 95 WWE was included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The mostly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, Epoxysqualene Biosynthesis Signaling, and Glutamate Degradation Signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In HGC prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.

中文翻译：

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确定癫痫女性多囊卵巢综合征的遗传因素：全基因组测序研究。

简介 患有癫痫 (WWE) 的女性更容易出现生殖内分泌疾病，尤其是多囊卵巢综合征 (PCOS)。本研究旨在探讨WWE中PCOS的遗传因素，以期提高个体精准诊断和治疗水平。方法2021年1月至2021年10月期间在华西医院注册的WWE纳入本研究。记录人口统计学和癫痫相关特征，并收集血液样本进行激素、葡萄糖代谢测试和全基因组测序。结果 在样本测序、质量控制和变异选择后，进行关联分析。进行通路分析以确定涉及的生物学通路。计算每个人的总体评分和 PCOS“负担评分”，以计算有害变异。这项研究总共纳入了 95 名 WWE 患者，其中 19 名患者被诊断患有 PCOS。患有 PCOS 的 WWE 显示出显着不同的激素分布和葡萄糖代谢受损的趋势。最相关的基因是 ZFYVE28、COL19A1、SIK3、ANKK1、PPIG 和 REPIN1。前 3 个经典途径是脂肪生成途径、环氧角鲨烯生物合成信号传导和谷氨酸降解信号传导。最显着的常见变异是位于基因 CELSR1 中的 rs11914038 和位于基因 ZBTB16 中的 rs651748。在 HGC 优先顺序中，ITGA9、PNPLA2 和 DAB2 是与已知 PCOS 基因距离最短的前 3 个基因。结论 葡萄糖和胰岛素代谢异常调节的遗传因素可能与 WWE 的 PCOS 合并症有关。在临床实践中应更加优先考虑针对这些过程的干预措施。