Background The decrease in sperm motility has a potent influence on fertilisation. Sperm motility, represented as the percentage of motile sperm in ejaculated sperms, is influenced by lifestyle habits or environmental factors and by inherited factors. However, genetic factors contributing to individual differences in sperm motility remain unclear. To identify genetic factors that influence human sperm motility, we performed a genome-wide association study (GWAS) of sperm motility.
Methods A two-stage GWAS was conducted using 811 Japanese men in a discovery stage, followed by a replication study using an additional 779 Japanese men.
Results In the two-staged GWAS, a single nucleotide polymorphism rs3791686 in the intron of gene for erb-b2 receptor tyrosine kinase 4 (ERBB4) on chromosome 2q34 was identified as a novel locus for sperm motility, as evident from the discovery and replication results using meta-analysis (β=−4.01, combined P=5.40×10−9).
Conclusions Together with the previous evidence that Sertoli cell-specific Erbb4-knockout mice display an impaired ability to produce motile sperm, this finding provides the first genetic evidence for further investigation of the genome-wide significant association at the ERBB4 locus in larger studies across diverse human populations.
- reproductive medicine
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YS and AT contributed equally.
Contributors YS and AT conceived, designed the experiments, performed the experiments and wrote the paper. TS performed the imputation analysis. SN, MY and TI prepared and collected samples. II contributed material and analysis tools. YS, AT, TS, II, AY and TI reviewed and revised the manuscript.
Funding 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, the European Union (BMH4-CT96-0314) (to TI), the Takeda Science Foundation (to AT) and The Suzuki Urinary Foundation (to YS).
Competing interests None declared.
Patient consent Obtained.
Ethics approval This study was approved by the ethics committees of the University of Tokushima and St. Marianna Medical University. All participants provided written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
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