Nat Commun. 2014 May 23;5:3857. doi: 10.1038/ncomms4857.
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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.
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Abstract
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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.
