• PMID: 24852083
• Gene Name: CDC42BPA
• Condition: Non-obstructive azoospermia (NOA), Male infertility
• Association: Associated
• Population size: 9513
• Population details: 9513 (3,608 NOA cases, 5,909 controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Non-obstructive azoospermia (NOA), Male infertility

Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men

Hu Z, Li Z, Yu J, Tong C, Lin Y, Guo X, Lu F, Dong J, Xia Y, Wen Y, Wu H, Li H, Zhu Y, Ping P, Chen X, Dai J, Jiang Y, Pan S, Xu P, Luo K, Du Q, Yao B, Liang M, Gui Y, Weng N, Lu H, Wang Z, Zhang F, Zhu X, Yang X, Zhang Z, Zhao H, Xiong C, Ma H, Jin G, Chen F, Xu J, Wang X, Zhou Z, Chen ZJ, Liu J, Shen H, Sha J.

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 × 10(-8)) at 6p21.32 (rs7194, P=3.76 × 10(-19)), 10q25.3 (rs7099208, P=6.41 × 10(-14)) and 6p12.2 (rs13206743, P=3.69 × 10(-8)), as well as one locus approaching genome-wide significance at 1q42.13 (rs3000811, P=7.26 × 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. FAU - Hu, Zhibin AU - Hu Z AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China [3]. FAU - Li, Zheng AU - Li Z AD - 1] Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China [2]. FAU - Yu, Jun AU - Yu J AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China [3]. FAU - Tong, Chao AU - Tong C AD - 1] Institute of Preventive Veterinary Medicine, Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China [2]. FAU - Lin, Yuan AU - Lin Y AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China [3]. FAU - Guo, Xuejiang AU - Guo X AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China [3]. FAU - Lu, Feng AU - Lu F AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Dong, Jing AU - Dong J AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Xia, Yankai AU - Xia Y AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Wen, Yang AU - Wen Y AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Wu, Hao AU - Wu H AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Li, Honggang AU - Li H AD - Family Planning Research Institute, Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China. FAU - Zhu, Yong AU - Zhu Y AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Ping, Ping AU - Ping P AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Chen, Xiangfeng AU - Chen X AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Dai, Juncheng AU - Dai J AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Jiang, Yue AU - Jiang Y AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Pan, Shandong AU - Pan S AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Xu, Peng AU - Xu P AD - Jinghua Hospital, Shenyang Dongfang Medical Group, Shenyang 110004, China. FAU - Luo, Kailing AU - Luo K AD - Reproductive Medical Center, The Second Hospital of Nanning, Nanning 530022, China. FAU - Du, Qiang AU - Du Q AD - Department of Reproduction, Shengjing Hospital, China Medical University, Shenyang 110004, China. FAU - Yao, Bing AU - Yao B AD - Department of Andrology, Nanjing Jinling Hospital, Nanjing 210029, China. FAU - Liang, Ming AU - Liang M AD - The Second Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Shandong 250033, China. FAU - Gui, Yaoting AU - Gui Y AD - Guangdong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, FuTian District, Shenzhen 518035, China. FAU - Weng, Ning AU - Weng N AD - Jinghua Hospital, Shenyang Dongfang Medical Group, Shenyang 110004, China. FAU - Lu, Hui AU - Lu H AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Wang, Zhuqing AU - Wang Z AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Zhang, Fengbin AU - Zhang F AD - The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China. FAU - Zhu, Xiaobin AU - Zhu X AD - Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Yang, Xiaoyu AU - Yang X AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. FAU - Zhang, Zhou AU - Zhang Z AD - Maternal and Child Health Hospital of Shanxi Province, Xian 300013, China. FAU - Zhao, Han AU - Zhao H AD - Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan 250021, China. FAU - Xiong, Chenliang AU - Xiong C AD - Family Planning Research Institute, Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China. FAU - Ma, Hongxia AU - Ma H AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Jin, Guangfu AU - Jin G AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Chen, Feng AU - Chen F AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Xu, Jianfeng AU - Xu J AD - Department of Urology, Huashan Hospital, Fudan University, Shanghai 200052, China. FAU - Wang, Xinru AU - Wang X AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Zhou, Zuomin AU - Zhou Z AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Chen, Zi-Jiang AU - Chen ZJ AD - Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan 250021, China. FAU - Liu, Jiayin AU - Liu J AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. FAU - Shen, Hongbing AU - Shen H AD - 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.