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

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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Figure 1: Genome-wide Manhattan plot for the GWAS meta-analysis.
Figure 2: Regional plots of the eight newly discovered PCOS loci.

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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).

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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.

Corresponding authors

Correspondence to Lin He or Zi-Jiang Chen.

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Shi, Y., Zhao, H., Shi, Y. et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 44, 1020–1025 (2012). https://doi.org/10.1038/ng.2384

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