Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome

• DOI: 10.1038/ng.2384
• Publication Date: 2012-08-12T18:23:11Z
• Authors: Yongyong Shi; Han Zhao; Yuhua Shi; Yunxia Cao; Dongzi Yang; Zhiqiang Li; Bo Zhang; Xiaoyan Liang; Tao Li; Jianhua Chen; Jiawei Shen; Junzhao Zhao; Li You; Xuan Gao; Dongyi Zhu; Xiaoming Zhao; Ying Yan; Yingying Qin; Wenjin Li; Junhao Yan; Qingzhong Wang; Junli Zhao; Ling Geng; Jinlong Ma; Yueran Zhao; Guang He; Aiping Zhang; Shuhua Zou; Aijun Yang; Jiayin Liu; Weidong Li; Baojie Li; Chunling Wan; Ying Qin; Juanzi Shi; Jing Yang; Hong Jiang; Jin-e Xu; Xiujuan Qi; Yun Sun; Yajie Zhang; Cuifang Hao; Xiuqing Ju; Dongni Zhao; Chun-e Ren; Xiuqing Li; Wei Zhang; Yiwen Zhang; Jiangtao Zhang; Di Wu; Changming Zhang; Lin He; Zi-Jiang Chen
• Keywords: Genotype; Validation Studies as Topic; Polymorphism, Single Nucleotide; 3. Good health; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Asian People; Diabetes Mellitus, Type 2; Gene Frequency; Meta-Analysis as Topic; Genetic Loci; Case-Control Studies; Humans; Receptors, FSH; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Polycystic Ovary Syndrome

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.