Abstract

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.

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Acknowledgements

We thank all participants involved in this study. This study was supported by grants from the National Basic Research Program of China (973 Program: 2012CB944700, 2010CB529600, 2011CB944502 and 2010CB945002), the 863 Program (2012AA02A515), the National Natural Science Foundation of China (81130022, 30973170, 81121001, 31000553, 81000238, 81070461 and 81000236), the National Key Technology Research and Development Program (2011BAI17B00), the Science Research Foundation Item of No-earnings Health Vocation (201002013), the Program for Changjiang Scholars and the Innovative Research Team in University (IRT1025), the Foundation for the Author of National Excellent Doctoral Dissertation of China (201026) and the Program for New Century Excellent Talents in University (NCET-09-0550).

Author information

Author notes

    • Yongyong Shi
    • , Han Zhao
    • , Yuhua Shi
    • , Yunxia Cao
    • , Dongzi Yang
    •  & Zhiqiang Li

    These authors contributed equally to this work.

Affiliations

  1. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

    • Yongyong Shi
    • , Zhiqiang Li
    • , Jianhua Chen
    • , Jiawei Shen
    • , Wenjin Li
    • , Qingzhong Wang
    • , Guang He
    • , Aiping Zhang
    • , Weidong Li
    • , Baojie Li
    • , Chunling Wan
    •  & Lin He
  2. Shanghai genomePilot Institutes for Genomics and Human Health, Shanghai, China.

    • Yongyong Shi
    • , Zhiqiang Li
    •  & Lin He
  3. Changning Mental Health Center, Shanghai, China.

    • Yongyong Shi
    •  & Zhiqiang Li
  4. Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, China.

    • Han Zhao
    • , Yuhua Shi
    • , Tao Li
    • , Li You
    • , Xuan Gao
    • , Yingying Qin
    • , Junhao Yan
    • , Ling Geng
    • , Jinlong Ma
    • , Yueran Zhao
    • , Jiangtao Zhang
    • , Di Wu
    • , Changming Zhang
    •  & Zi-Jiang Chen
  5. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China.

    • Han Zhao
    • , Yuhua Shi
    • , Li You
    • , Xuan Gao
    • , Yingying Qin
    • , Junhao Yan
    • , Ling Geng
    • , Jinlong Ma
    • , Yueran Zhao
    • , Jiangtao Zhang
    • , Di Wu
    • , Changming Zhang
    •  & Zi-Jiang Chen
  6. The Key Laboratory for Reproductive Endocrinology, Ministry of Education of the People's Republic of China, Jinan, China.

    • Han Zhao
    • , Yuhua Shi
    • , Li You
    • , Xuan Gao
    • , Yingying Qin
    • , Junhao Yan
    • , Ling Geng
    • , Jinlong Ma
    • , Yueran Zhao
    •  & Zi-Jiang Chen
  7. Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.

    • Han Zhao
    • , Yuhua Shi
    • , Li You
    • , Xuan Gao
    • , Yingying Qin
    • , Junhao Yan
    • , Ling Geng
    • , Jinlong Ma
    • , Yueran Zhao
    •  & Zi-Jiang Chen
  8. Reproductive Medicine Center, The First Affiliated Hospital, Anhui Medical University, Hefei, China.

    • Yunxia Cao
  9. Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

    • Dongzi Yang
  10. Reproductive Medicine Center, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

    • Bo Zhang
  11. Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

    • Xiaoyan Liang
  12. Shanghai Institute of Mental Health, Shanghai, China.

    • Jianhua Chen
  13. Reproductive Medicine Unit, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.

    • Junzhao Zhao
  14. Reproductive Medicine Center, Linyi People's Hospital, Linyi, China.

    • Dongyi Zhu
  15. Center for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Xiaoming Zhao
    • , Yun Sun
    •  & Zi-Jiang Chen
  16. National Institute of Hospital Administration, Ministry of Health of the People's Republic of China, Beijing, China.

    • Ying Yan
  17. Reproductive Medicine Center, Affiliated Hospital of Ningxia Medical University, Yinchuan, China.

    • Junli Zhao
  18. Center for Reproductive Medicine, Qingdao Women & Children Medical Healthcare Center, Qingdao, China.

    • Shuhua Zou
  19. Reproductive Medicine Center, Affiliated Hospital of Jining Medical College, Jining, China.

    • Aijun Yang
  20. Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

    • Jiayin Liu
  21. Oncology Translational Medicine, GlaxoSmithKline R&D China, Shanghai, China.

    • Ying Qin
  22. Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shaanxi Province, Xi'an, China.

    • Juanzi Shi
  23. Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China.

    • Jing Yang
  24. Department of Obstetrics and Gynecology, 105th Hospital of People's Liberation Army, Hefei, China.

    • Hong Jiang
  25. Department of Obstetrics and Gynecology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, China.

    • Jin-e Xu
    •  & Xiujuan Qi
  26. Department of Obstetrics and Gynecology, Jinan Health Institute of Maternity and Infant, Jinan, China.

    • Yajie Zhang
  27. Reproductive Medical Center, Yantai Yuhuangding Hospital, Yantai, China.

    • Cuifang Hao
  28. Department of Obstetrics and Gynecology, Tengzhou People's Hospital, Tengzhou, China.

    • Xiuqing Ju
  29. Reproductive Medical Center, Shengjing Hospital of China Medical University, Shenyang, China.

    • Dongni Zhao
  30. Department of Obstetrics and Gynecology, Affiliated Hospital of Weifang Medical College, Weifang, China.

    • Chun-e Ren
  31. Department of Obstetrics and Gynecology, Anqiu People's Hospital, Anqiu, China.

    • Xiuqing Li
  32. Department of Gynecology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.

    • Wei Zhang
  33. Reproductive Medicine Unit, Weihai Women and Children Hospital, Weihai, China.

    • Yiwen Zhang
  34. Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

    • Lin He
  35. Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

    • Lin He
  36. Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.

    • Zi-Jiang Chen

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Contributions

Z.-J.C., L.H. and Yongyong Shi designed the whole study. Yongyong Shi supervised the experiments and data analysis. Z.-J.C. supervised patient diagnosis and sample recruitment. Yongyong Shi, Z.L., H.Z., T.L. and J. Shen conducted data analyses and drafted the manuscript. H.Z., Yuhua Shi, L.G., J.M., Yingying Qin and J. Yan recruited samples. Y.C., D.Y., B.Z., X. Liang, Junzhao Zhao, D. Zhu, X.Z., Y.Y., Junli Zhao, S.Z., A.Y., J.L., J. Shi, J. Yang, H.J., J.X., X.Q., Y. Sun, Yajie Zhang, C.H., X.J., D. Zhao, C.R., X. Li, W.Z. and Yiwen Zhang coordinated and provided samples from different hospitals. J.C., Wenjin Li, Q.W., G.H., A.Z., Weidong Li, C.W., B.L. and Ying Qin performed or contributed to the main experiments. L.Y., Y. Zhao, D.W. and C.Z. performed DNA extraction. X.G and J.Z. performed endocrine biochemical examination. All authors critically reviewed the manuscript and approved the final version.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Lin He or Zi-Jiang Chen.

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DOI

https://doi.org/10.1038/ng.2384

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