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.
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We are grateful to the late Prof. Yutaka Nakahori and Profs. Eitetsue Koh, Jiro Kanaya, Mikio Namiki, Kiyomi Matsumiya, Akira Tsujimura, Kiyoshi Komatsu, Naoki Itoh, and Jiro Eguchi for collecting blood samples from participants. We also thank Prof. Toyomasa Katagiri for his assistance with the AB GeneAmp PCR system 9700. This study was supported in part by the Ministry of Health and Welfare of Japan (1013201) (to TI), Grant-in-Aids for Scientific Research (C) (26462461) (to YS), (23510242) (to AT), and Grant-in-Aids for Scientific Research (B) (17H04331) (to YS), (15H04320) (to AT) from the Japan Society for the Promotion of Science, and the European Union (BMH4-CT96-0314) (to TI). We would like to thank Editage (www.editage.com) for English language editing.
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Sato, Y., Tajima, A., Kiguchi, M. et al. Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels. J Hum Genet 65, 683–691 (2020). https://doi.org/10.1038/s10038-020-0757-3