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

作者：Hu, Zhibin^*; Li, Zheng; Yu, Jun; Tong, Chao; Lin, Yuan; Guo, Xuejiang; Lu, Feng; Dong, Jing; Xia, Yankai; Wen, Yang; Wu, Hao; Li, Honggang; Zhu, Yong; Ping, Ping; Chen, Xiangfeng; Dai, Juncheng; Jiang, Yue; Pan, Shandong; Xu, Peng; Luo, Kailing; Du, Qiang; Yao, Bing; Liang, Ming; Gui, Yaoting; Weng, Ning; Lu, Hui; Wang, Zhuqing; Zhang, Fengbin; Zhu, Xiaobin; Yang, Xiaoyu; Zhang, Zhou; Zhao, Han; Xiong, Chenliang; Ma, Hongxia; Jin, Guangfu; Chen, Feng; Xu, Jianfeng; Wang, Xinru

来源：Nature Communications, 2014, 5(1): 3857.

DOI：10.1038/ncomms4857

• GENOME-WIDE ASSOCIATION
• MALE-INFERTILITY
• LINEAGE
• GENE
• DISTINCT
• REVEALS
• PROTEIN
• REGION
• TESTIS

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.

• 出版日期2014-5
• 单位复旦大学; 上海交通大学; 山东大学; 中国医科大学; 华中科技大学; 南宁市第二人民医院; 山东省立医院; 生殖医学国家重点实验室; 北京大学; 山东中医药大学; 浙江大学; 南京医科大学