机构：[1]State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China[2]Department of Epidemiology and Biostatistics and KeyLaboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China[3]Shanghai HumanSperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China[4]Department of Histologyand Embryology, Nanjing Medical University, Nanjing 210029, China[5]Institute of Preventive Veterinary Medicine, Zhejiang Provincial Key Laboratory ofPreventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China[6]Department of Toxicology and Key Laboratory of Modern Toxicology ofMinistry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China[7]Family Planning Research Institute, Center of ReproductiveMedicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China[8]Jinghua Hospital, Shenyang Dongfang MedicalGroup, Shenyang 110004, China[9]Reproductive Medical Center, The Second Hospital of Nanning, Nanning 530022, China[10]Department of Reproduction,Shengjing Hospital, China Medical University, Shenyang 110004, China中国医科大学附属盛京医院[11]Department of Andrology, Nanjing Jinling Hospital, Nanjing 210029, China[12]TheSecond Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Shandong 250033, China[13]Guangdong Key Laboratory of MaleReproductive Medicine and Genetics, Peking University Shenzhen Hospital, FuTian District, Shenzhen 518035, China北京大学深圳医院深圳医学信息中心[14]The Women’s Hospital, School ofMedicine, Zhejiang University, Hangzhou 310006, China浙江大学医学院附属妇产科医院[15]Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University,Nanjing 210029, China江苏省人民医院[16]Maternal and Child Health Hospital of Shanxi Province, Xian 300013, China[17]Center for Reproductive Medicine, ShandongProvincial Hospital, Shandong University, Jinan 250021, China[18]Department of Urology, Huashan Hospital, Fudan University, Shanghai 200052, China
Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. Our previous genome-wide association study (GWAS) identified three susceptibility loci for NOA in Han Chinese men. Here we test promising associations in an extended three-stage validation using 3,608 NOA cases and 5,909 controls to identify additional risk loci. We find strong evidence of three NOA susceptibility loci (P<5.0 x 10(-8)) at 6p21.32 (rs7194, P=3.76 x 10(-19)), 10q25.3 (rs7099208, P=6.41 x 10(-14)) and 6p12.2 (rs13206743, P=3.69 x 10(-8)), as well as one locus approaching genome-wide significance at 1q42.13 (rs3000811, P=7.26 x 10(-8)). In addition, we investigate the phenotypic effect of the related gene (gek, orthologous to CDC42BPA) at 1q42.13 on male fertility using a Drosophila model. These results advance our understanding of the genetic susceptibility to NOA and provide insights into its pathogenic mechanism.
基金：
National Key Basic Research ProgramNational Basic Research Program of China [2013CB945700, 2011CB944304, 2013CB911400, 2011CB944504, 2012CB966600, 2010CB945200]; Chinese Natural Science FundsNational Natural Science Foundation of China [81222006]; National Science Foundation for Distinguished Young Scholars of China - Priority Academic Program Development of Jiangsu Higher Education Institutions [81225020]; Key Project of Shanghai Municipal Science and Technology [10JC1409900]
第一作者机构：[1]State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China[2]Department of Epidemiology and Biostatistics and KeyLaboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China[2]Department of Epidemiology and Biostatistics and KeyLaboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China[4]Department of Histologyand Embryology, Nanjing Medical University, Nanjing 210029, China[15]Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University,Nanjing 210029, China
推荐引用方式(GB/T 7714)：
Zhibin Hu,Zheng Li,Jun Yu,et al.Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men[J].NATURE COMMUNICATIONS.2014,5:doi:10.1038/ncomms4857.
APA：
Zhibin Hu,Zheng Li,Jun Yu,Chao Tong,Yuan Lin...&Jiahao Sha.(2014).Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men.NATURE COMMUNICATIONS,5,
MLA：
Zhibin Hu,et al."Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men".NATURE COMMUNICATIONS 5.(2014)
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