关联分析鉴定中国男性非梗阻性无精子症的新风险基因座。
Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men.
机构信息
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].
1] Shanghai Human Sperm Bank, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China [2].
出版信息
Nat Commun. 2014 May 23;5:3857. doi: 10.1038/ncomms4857.
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.
男性因素不育影响全球六分之一的夫妇，而非阻塞性无精子症（NOA）是最严重的形式之一。我们之前的全基因组关联研究（GWAS）确定了汉族男性 NOA 的三个易感基因座。在这里，我们使用 3608 例 NOA 病例和 5909 例对照进行了扩展的三阶段验证，以测试有前途的关联，以确定其他风险基因座。我们发现了 6p21.32（rs7194，P=3.76×10(-19))、10q25.3(rs7099208，P=6.41×10(-14))和 6p12.2(rs13206743，P=3.69×10(-8))三个与 NOA 易感性相关的强证据（P<5.0×10(-8))，以及在 1q42.13(rs3000811，P=7.26×10(-8))处接近全基因组显著性的一个基因座。此外，我们使用果蝇模型研究了 1q42.13 处相关基因（与 CDC42BPA 同源的 gek）对男性生育力的表型影响。这些结果提高了我们对 NOA 遗传易感性的理解，并为其发病机制提供了新的见解。
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