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

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 â ̂'14) and 6p12.2 (rs13206743, P=3.69 × 10 â ̂'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.

Original languageEnglish (US)
Article number3857
JournalNature Communications
Volume5
DOIs
StatePublished - May 23 2014
Externally publishedYes

Fingerprint

Azoospermia
loci
Genes
genome
magnetic permeability
fertility
Drosophila
genes
Genome-Wide Association Study
Male Infertility
Genetic Predisposition to Disease
Fertility
Genome

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men. / 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; Zhou, Zuomin; Chen, Zi Jiang; Liu, Jiayin; Shen, Hongbing; Sha, Jiahao.

In: Nature Communications, Vol. 5, 3857, 23.05.2014.

Research output: Contribution to journalArticle

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 2014, 'Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men', Nature Communications, vol. 5, 3857. https://doi.org/10.1038/ncomms4857
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 ; Zhou, Zuomin ; Chen, Zi Jiang ; Liu, Jiayin ; Shen, Hongbing ; Sha, Jiahao. / Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men. In: Nature Communications. 2014 ; Vol. 5.
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abstract = "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 {\^a} ̂'14) and 6p12.2 (rs13206743, P=3.69 × 10 {\^a} ̂'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.",
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AU - Hu, Zhibin

AU - Li, Zheng

AU - Yu, Jun

AU - Tong, Chao

AU - Lin, Yuan

AU - Guo, Xuejiang

AU - Lu, Feng

AU - Dong, Jing

AU - Xia, Yankai

AU - Wen, Yang

AU - Wu, Hao

AU - Li, Honggang

AU - Zhu, Yong

AU - Ping, Ping

AU - Chen, Xiangfeng

AU - Dai, Juncheng

AU - Jiang, Yue

AU - Pan, Shandong

AU - Xu, Peng

AU - Luo, Kailing

AU - Du, Qiang

AU - Yao, Bing

AU - Liang, Ming

AU - Gui, Yaoting

AU - Weng, Ning

AU - Lu, Hui

AU - Wang, Zhuqing

AU - Zhang, Fengbin

AU - Zhu, Xiaobin

AU - Yang, Xiaoyu

AU - Zhang, Zhou

AU - Zhao, Han

AU - Xiong, Chenliang

AU - Ma, Hongxia

AU - Jin, Guangfu

AU - Chen, Feng

AU - Xu, Jianfeng

AU - Wang, Xinru

AU - Zhou, Zuomin

AU - Chen, Zi Jiang

AU - Liu, Jiayin

AU - Shen, Hongbing

AU - Sha, Jiahao

PY - 2014/5/23

Y1 - 2014/5/23

N2 - 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 â ̂'14) and 6p12.2 (rs13206743, P=3.69 × 10 â ̂'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.

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