多囊卵巢综合征多祖先全基因组关联分析，这一成果由上海交通大学师咏勇课题组经过不懈努力而取得。该项研究成果发表在2025年11月4日出版的《自然—遗传学》上。

在这里，小组对12419名中国多囊卵巢综合征女性和34235名对照进行了全基因组关联研究，随后对多达13773名欧洲病例和411088名对照进行了多祖先荟萃分析，确定了94个独立位点，其中73个以前未报道过。尽管进化压力不同，但中国人和欧洲人的祖先显示出大量的遗传重叠。综合功能分析优先考虑了在特定组织中控制基因活性的调节变异，包括抗勒氏杆菌激素（AMH）在内的疾病引导基因，以及涉及配体结合域相互作用和过氧化物酶体增殖体激活受体γ (PPARG)信号传导的生物学途径。课题组人员发现颗粒细胞在多囊卵巢综合征的发展中特别重要。他们的基因驱动药物发现方法揭示了多种药物靶点和重新利用的机会，使个性化治疗策略成为可能。这些结果增强了他们对多囊卵巢综合征分子基础的认识，为精准医疗铺平了道路。

研究人员表示，多囊卵巢综合征（PCOS）是育龄妇女的主要内分泌疾病，具有高度遗传性，但其多基因结构尚不清楚。

附：英文原文

Title: Multi-ancestry genome-wide association analyses of polycystic ovary syndrome

Author: Zhao, Han, Xu, Yuping, Xue, Baiqiang, Zhao, Shigang, Zhang, Manfei, Wu, Xiao-Ke, Wang, Tianjuan, Wen, Yanqin, Li, Shumin, Zhang, Qing, Yang, Ziyi, Sun, Hui, Pan, Ting, Lian, Yihong, Gao, Xueying, Gao, Chengwen, Wang, Zhao, Wu, Chuanhong, Zhang, Changming, Jian, Xuemin, Peng, Lixia, Zhang, Xin, Wang, Baokun, Wei, Lieqing, He, Yuyan, Xia, Disong, Wu, Ziyun, Yang, Qiangzhen, Sun, Yuanchao, Ding, Yonghe, Du, Siyuan, Xia, Guofeng, Jing, Yulong, Xu, Hairong, Shi, Weiye, Liu, Junting, He, Lin, Chen, Zi-Jiang, Cao, Yunxia, Li, Zhiqiang, Shi, Yongyong

Issue&Volume: 2025-11-04

Abstract: Polycystic ovary syndrome (PCOS), the leading endocrine disorder in women of reproductive age, is highly heritable, yet its polygenic architecture remains poorly understood. Here we conducted a genome-wide association study on 12,419 Chinese women with PCOS and 34,235 controls, followed by a multi-ancestry meta-analysis with up to 13,773 European cases and 411,088 controls, identifying 94 independent loci, 73 of which were previously unreported. Despite different evolutionary pressures, Chinese and European ancestries showed substantial genetic overlap. Integrative functional analyses prioritized regulatory variants controlling gene activity in specific tissues, disease-causing genes including anti-Müllerian hormone (AMH), and biological pathways involving ligand-binding domain interactions and peroxisome proliferator-activated receptor gamma (PPARG) signaling. We identified granulosa cells as particularly important in PCOS development. Our genetics-driven drug discovery approach revealed multiple drug targets and repurposing opportunities, enabling personalized treatment strategies. These results enhance our understanding of the molecular basis of PCOS, paving the way for precision medicine.

DOI: 10.1038/s41588-025-02393-x

Source: https://www.nature.com/articles/s41588-025-02393-x