PT - JOURNAL ARTICLE AU - Sato, Youichi AU - Tajima, Atsushi AU - Sato, Takehiro AU - Nozawa, Shiari AU - Yoshiike, Miki AU - Imoto, Issei AU - Yamauchi, Aiko AU - Iwamoto, Teruaki TI - Genome-wide association study identifies <em>ERBB4</em> on 2q34 as a novel locus associated with sperm motility in Japanese men AID - 10.1136/jmedgenet-2017-104991 DP - 2018 Jun 01 TA - Journal of Medical Genetics PG - 415--421 VI - 55 IP - 6 4099 - http://jmg.bmj.com/content/55/6/415.short 4100 - http://jmg.bmj.com/content/55/6/415.full SO - J Med Genet2018 Jun 01; 55 AB - 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.