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, Z.J., Liu, J., Shen, H., Sha, J. (2014). Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men.  Nat. Commun. 5(): 3857.

FBrf0225129

Research paper

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.