Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identified ERBB4 at 2q34 as a genetic locus associated with sperm motility. However, GWASs for human semen volume and sperm concentration have not been conducted. In addition, testis size also reportedly correlates with semen quality, and it is important to identify genes that affect testis size. Reproductive hormones also play an important role in spermatogenesis. To date, genetic loci associated with plasma testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels have been identified using GWASs. However, GWASs have not identified any relevant loci for plasma inhibin B levels. We conducted a two-stage GWAS using 811 Japanese men in a discovery stage followed by a replication stage using an additional 721 Japanese men. The results of the discovery and replication stages were combined into a meta-analysis. After setting a suggestive significance threshold for P values < 5 × 10-6　in the discovery stage, we identified ten regions with SNPs (semen volume: one, sperm concentration: three, testes size: two, and inhibin B: four). We selected only the most significant SNP in each region for replication genotyping. Combined discovery and replication results in the meta-analysis showed that the locus 12q21.31 associated with plasma inhibin B levels (rs11116724) had the most significant association (P = 5.7 × 10-8). The LRRIQ1 and TSPAN19 genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels.

中文翻译：

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精液量，精子浓度，睾丸大小和血浆中抑制素B水平的全基因组关联研究。

精液质量受环境因素，内分泌功能异常和遗传因素影响。GWAS最近将2q34的ERBB4鉴定为与精子运动相关的遗传位点。但是，尚未进行用于人类精液量和精子浓度的GWAS。另外，据报道睾丸的大小也与精液质量有关，因此鉴定影响睾丸大小的基因很重要。生殖激素在精子发生中也起重要作用。迄今为止，已经使用GWAS鉴定了与血浆睾丸激素，性激素结合球蛋白（SHBG），促卵泡激素（FSH）和促黄体生成激素（LH）水平相关的遗传基因座。但是，GWAS尚未发现血浆抑制素B水平的任何相关基因座。我们在发现阶段使用811名日本人进行了两阶段的GWAS，然后使用了另外721名日本人进行了复制阶段。发现和复制阶段的结果被合并到荟萃分析中。在发现阶段为P值<5×10-6设置暗示显着性阈值后，我们确定了十个具有SNP的区域（精液量：一个，精子浓度：三个，睾丸大小：两个，抑制素B：四个）。我们仅选择每个区域中最重要的SNP进行复制基因分型。荟萃分析的综合发现和复制结果表明，与血浆抑制素B水平相关的基因座12q21.31（rs11116724）具有最显着的相关性（P = 5.7×10-8）。LRRIQ1和TSPAN19基因位于12q21.31区域。