title: Lack of replication of four candidate SNPs implicated in human male fertility traits: a large-scale population-based study.
abstract: OBJECTIVE
  Are the four candidate loci (rs7867029, rs12870438, rs7174015 and rs724078) for human male fertility traits, identified in a genome-wide association study (GWAS) of a Hutterite population in the USA, associated with semen quality traits in a Japanese population?
  
  
  CONCLUSIONS
  The four single nucleotide polymorphisms (SNPs) rs7867029, rs12870438, rs7174015 and rs724078 have no association with semen parameters in a meta-analysis of two Japanese male cohorts.
  
  
  BACKGROUND
  Four (rs7867029, rs12870438, rs7174015 and rs724078) of the SNPs associated with family size or birth rate in the GWAS of a Hutterite population in the USA were associated with semen parameters in ethnically diverse men from Chicago, USA.
  
  
  METHODS
  This is a replication study in a total of 2015 Japanese subjects, including 791 fertile men and 1224 young men from the general population.
  
  
  METHODS
  We performed a replication study in two cohorts to assess whether the SNPs rs7867029, rs12870438, rs7174015 and rs724078 are associated with sperm concentration, semen volume, total sperm numbers, total motile sperm numbers or sperm motility. The rs12870438 SNP was detected by restriction fragment length polymorphism PCR while rs7174015, rs724078 and rs7867029 SNPs were genotyped using TaqMan probes.
  
  
  RESULTS
  This study indicated that none of the four SNPs rs7867029, rs12870438, rs7174015 and rs724078 displayed a significant association with semen parameters in the meta-analysis of two Japanese male cohorts.
  
  
  CONCLUSIONS
  Only four SNPs identified in the Hutterite GWAS were examined for associations with semen quality traits in a Japanese population. In addition, the linkage disequilibrium structures around the testing markers were different between ethnic groups.
  
  
  CONCLUSIONS
  Locus mapping studies using a set of tagging SNPs across the loci will be necessary in populations with larger sample sizes in order to understand the contribution of specific genes to semen quality.
  This study was supported in part by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (23510242) (to A.Ta.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T.I.), and the Takeda Science Foundation (to A.Ta.). None of the authors has any competing interests to declare.
authors.affiliation: Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan youichi.sato@tokushima-u.ac.jp atajima@med.kanazawa-u.ac.jp.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-8640, Japan youichi.sato@tokushima-u.ac.jp atajima@med.kanazawa-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.affiliation: Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Tsunematsu
authors.affiliation: Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors.forename: Shiari
authors.initials: S
authors.lastname: Nozawa
authors.affiliation: Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yoshiike
authors.affiliation: Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan.
authors.forename: Eitetsue
authors.initials: E
authors.lastname: Koh
authors.affiliation: Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kanaya
authors.affiliation: Department of Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8641, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.affiliation: Department of Urology, Osaka Police Hospital, Osaka, 543-0035, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Matsumiya
authors.affiliation: Department of Urology, Graduate School of Medicine, Faculty of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.affiliation: Department of Urology, Harasanshinkai Hospital, Fukuoka, 812-0033, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Komatsu
authors.affiliation: Department of Urology, Sapporo Medical University, Sapporo, 060-8543, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Itoh
authors.affiliation: Department of Urology, Nagasaki University, Nagasaki, 852-8523, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Eguchi
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.affiliation: Department of Pharmaceutical Information Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8505, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan Center for Infertility and IVF, International University of Health and Welfare Hospital, Nasushiobara, 329-2763, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D000328:Adult; D001213:Asian / Q000235:genetics*; D015331:Cohort Studies; D005298:Fertility / Q000235:genetics*; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055101:Semen Analysis; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics; D014481:United States
chemical_list: D005819:Genetic Markers
keywords: Japanese population; male fertility; replication study; semen quality