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Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3

Nature Genetics volume 43, pages 55–59 (2011)Cite this article

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Abstract

Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis Pmeta = 7.55 × 10−21, odds ratio (OR) 0.71); 2p21 (rs13429458, Pmeta = 1.73 × 10−23, OR 0.67); and 9q33.3 (rs2479106, Pmeta = 8.12 × 10−19, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.

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Figure 1: Genome-wide association scan for PCOS.
Figure 2: Regional plots of the three newly discovered PCOS loci (2p16.3, 2p21 and 9q33.3).

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  • 28 January 2011

    In the version of this article originally posted online corresponding author Yongyong Shi was not designated as a corresponding author. This error has been corrected in the HTML version of the paper.

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Acknowledgements

We thank all participants involved in this study. We thank J. Simpson for revising this manuscript and X. Xu, X. Xing, T. Li, M. Guo, L. Cui, Q. Zheng, C. Li, J. Zhang, D. Wu, C. Zhang, X. Yan, W. He, Y. Cui, M. Xia, J. Li, P. Wang, H. Lv, S. Xu and L. Wang for subject recruitment. This study was supported by grants from the National Basic Research Program of China (973 Program-2006CB944004, 2010CB945000, 2007CB947403, 2007CB914703, 2007CB947300, 2010CB529600), the National 863 Project of China grants (2006AA02A407, 2009AA022701), the National Natural Science Foundation of China (30973170) and the Shanghai Municipal Commission of Science and Technology Program (09DJ1400601).

Author information

Author notes

  1. Han Zhao, Lin He and Yuhua Shi: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China

    Zi-Jiang Chen, Han Zhao, Yuhua Shi, Yingying Qin, Li You, Yuehong Bian, Xuan Gao, Ling Geng, Junhao Yan, Yuan Li, Jinlong Ma & Yueran Zhao

  2. Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China.,

    Zi-Jiang Chen, Han Zhao, Yuhua Shi, Yingying Qin, Li You, Yuehong Bian, Xuan Gao, Ling Geng, Junhao Yan, Yuan Li, Jinlong Ma & Yueran Zhao

  3. Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Lin He

  4. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China

    Lin He, Yongyong Shi & Zhiqiang Li

  5. Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Lin He

  6. Affiliated Hospital of Ningxia Medical University, Ningxia, China

    Junli Zhao

  7. The First Affiliated Hospital with Nanjing Medical University, Jiangsu, China

    Jiayin Liu

  8. The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong, China

    Xiaoyan Liang

  9. Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    Xiaoming Zhao

  10. The First Affiliated Hospital of Wenzhou Medical College, Zhejiang, China

    Junzhao Zhao

  11. The First Affiliated Hospital of Zhengzhou University, Henan, China

    Yingpu Sun

  12. Maternal and Child Health Hospital in Guangxi, Guangxi, China

    Bo Zhang

  13. 105th Hospital of People's Liberation Army, Anhui, China

    Hong Jiang

  14. Shengjing Hospital of China Medical University, Liaoning, China

    Dongni Zhao

  15. Qingdao Women & Children Medical Healthcare Center, Shandong, China

    Yiran Li

  16. Affiliated Hospital of Weifang Medical College, Shandong, China

    Yiran Li & Chun-e Ren

  17. Linyi People's Hospital, Shandong, China

    Dongyi Zhu

  18. Shandong Jingning First People's Hospital, Shandong, China

    Xiuqin Sun

  19. The Affiliated Hospital of Medical College Qingdao University, Shandong, China

    Jin-e Xu

  20. Yantai Yuhuangding Hospital, Shandong, China

    Cuifang Hao

  21. Jinan Health Institute of Maternity and Infant, Shandong, China

    Yajie Zhang

  22. Nanfang Hospital, Guangdong, China

    Shiling Chen

  23. Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China

    Wei Zhang

  24. Affiliated Hospital of Jining Medical College, Shandong, China

    Aijun Yang

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  1. Zi-Jiang Chen
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Contributions

Z.-J.C., L.H. and Yongyong Shi designed the study and revised the manuscript. Z.-J.C. supervised patients' diagnosis, subject recruitment and performance of experiments. Yongyong Shi supervised the experiments and data analysis. H.Z. and Z.L. conducted data analyses and drafted the manuscript. H.Z., Yuhua Shi, Y.Q., L.Y., L.G. and J.Y. recruited subjects. Junli Zhao, J.L., X.L., X.Z., Junzhao Zhao, Y. Sun, B.Z., H.J., D. Zhao, Yiran Li, D. Zhu, X.S., J.-e.X., C.H., C.-e.R., Y. Zhang, S.C., W.Z. and A.Y. coordinated and provided samples from different hospitals. L.Y., Y.B., Yuan Li, J.M. and Y. Zhao performed DNA extraction. X.G. performed endocrine biochemical examination. All authors critically reviewed the article and approved the final manuscript.

Corresponding authors

Correspondence to Zi-Jiang Chen or Yongyong Shi.

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The authors declare no competing financial interests.

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Chen, ZJ., Zhao, H., He, L. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 43, 55–59 (2011). https://doi.org/10.1038/ng.732

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