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A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia

Nature Genetics volume 44, pages 183–186 (2012)Cite this article

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Abstract

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility. Its pathophysiology is largely unknown, and few genetic influences have been defined. To identify common variants contributing to NOA in Han Chinese men, we performed a three-stage genome-wide association study of 2,927 individuals with NOA and 5,734 controls. The combined analyses identified significant (P < 5.0 × 10−8) associations between NOA risk and common variants near PRMT6 (rs12097821 at 1p13.3: odds ratio (OR) = 1.25, P = 5.7 × 10−10), PEX10 (rs2477686 at 1p36.32: OR = 1.39, P = 5.7 × 10−12) and SOX5 (rs10842262 at 12p12.1: OR = 1.23, P = 2.3 × 10−9). These findings implicate genetic variants at 1p13.3, 1p36.32 and 12p12.1 in the etiology of NOA in Han Chinese men.

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Figure 1: Genome-wide association results for NOA in Han Chinese men.
Figure 2: Regional plots of the four identified marker SNPs based on imputation results using the Han Chinese in Beijing (CHB) and Japanese in Tokyo (JPT) reference sets from the 1000 Genomes Project database (June 2010 release).

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Acknowledgements

The authors wish to thank all the study participants, research staff and students who participated in this work. We thank Q. Wei (MD Anderson Cancer Center) for editing the manuscript. This work was funded by the National Key Basic Research Program Grant (2011CB944304) and the China National High-Tech Research and Development Program Grant (2009AA022705) and partly by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Author notes

  1. Zhibin Hu, Yankai Xia and Xuejiang Guo: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

    Zhibin Hu, Yankai Xia, Xuejiang Guo, Yibo Wu, Xiaoyu Yang, Jiayin Liu, Zuomin Zhou, Hongbing Shen, Xinru Wang & Jiahao Sha

  2. Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

    Zhibin Hu, Juncheng Dai, Yue Jiang, Feng Lu, Huizhang Li & Hongbing Shen

  3. Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

    Yankai Xia, Chuncheng Lu & Xinru Wang

  4. Department of Histology and Embryology, Nanjing Medical University, Nanjing, China

    Xuejiang Guo, Yibo Wu, Zuomin Zhou & Jiahao Sha

  5. Family Planning Research Institute, Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    HongGang Li & Chenliang Xiong

  6. Sperm Development and Genetics Laboratory, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Hongliang Hu & Zheng Li

  7. Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Hongliang Hu & Zheng Li

  8. Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China

    Xiaoyu Yang & Jiayin Liu

  9. Department of Andrology, Nanjing Jinling Hospital, Nanjing, China

    Bing Yao

  10. Guangdong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, FuTian District, Shenzhen, China.,

    Yaoting Gui

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Contributions

J.S., X.W. and H.S. directed the study, obtained financial support and were responsible for study design, interpretation of results and manuscript writing. Z.H. performed overall project management along with Y.X. and X.G., performed statistical analyses along with J.D. and drafted the initial manuscript. Y.J., F.L. and H.L. were responsible for sample processing and managed the genotyping data. X.Y., Y.W., J.L., B.Y., C.L. and Z.Z. were responsible for subject recruitment and sample preparation for the Nanjing samples. H.L., Y.G. and C.X. were responsible for subject recruitment and sample preparation for the Wuhan samples. H.H. and Z.L. were responsible for subject recruitment and sample preparation for the Shanghai samples. All authors approved the final manuscript.

Corresponding authors

Correspondence to Hongbing Shen, Xinru Wang or Jiahao Sha.

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The authors declare no competing financial interests.

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Hu, Z., Xia, Y., Guo, X. et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nat Genet 44, 183–186 (2012). https://doi.org/10.1038/ng.1040

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