Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels
Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels
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精液量、精子浓度、睾丸大小和血浆抑制素 B 水平的全基因组关联研究
DOI：
10.1038/s10038-020-0757-3
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发表时间：
2020
影响因子：
3.5
通讯作者：
Iwamoto Teruaki
中科院分区：
文献类型：
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作者：
Sato Youichi;Tajima Atsushi;Kiguchi Misaki;Kogusuri Suzu;Fujii Aki;Sato Takehiro;Nozawa Shiari;Yoshiike Miki;Mieno Makiko;Kojo Kosuke;Uchida Masahiro;Tsuchiya Haruki;Yamasaki Kazumitu;Imoto Issei;Iwamoto Teruaki
精液质量受环境因素、内分泌功能异常和遗传因素的影响。GWAS最近发现ERBB 4在2 q34作为一个与精子活力相关的遗传位点。然而，尚未进行人类精液量和精子浓度的GWAS。此外，据报道，睾丸大小也与精液质量相关，重要的是要确定影响睾丸大小的基因。生殖激素在精子发生中也起重要作用。到目前为止，已经使用GWAS确定了与血浆睾酮、性激素结合球蛋白（SHBG）、卵泡刺激素（FSH）和黄体生成素（LH）水平相关的遗传位点。然而，GWAS尚未鉴定出任何与血浆β-受体结合素B水平相关的基因座。我们进行了两个阶段的GWAS使用811名日本男性在一个发现阶段，然后复制阶段使用额外的721名日本男性。将发现和复制阶段的结果合并为荟萃分析。在发现阶段设定P值< 5 × 10− 6的提示性显著性阈值后，我们确定了10个SNP区域（精液量：1个，精子浓度：3个，睾丸大小：2个，睾丸素B：4个）。我们仅选择每个区域中最重要的SNP进行复制基因分型。荟萃分析中的发现和重复结果显示，与血浆中的B水平相关的基因座12q21.31（rs 11116724）具有最显著的相关性（P= 5.7 × 10−8）。LRRIQ 1和TSPAN 19基因位于12q21.31区域。这项研究提供了新的易感性的变化，有助于血浆中的reflectin B水平。
Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identifiedERBB4at 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 forPvalues < 5 × 10−6in 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). TheLRRIQ1andTSPAN19genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels.