title: Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.
abstract: BACKGROUND
  Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).
  
  
  OBJECTIVE
  To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia.
  
  
  METHODS
  A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011.
  
  
  METHODS
  We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.
  
  
  CONCLUSIONS
  Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P  =  0.005, 95%CI 1.58-13.4) and 1.82 (P  =  0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings.
  
  
  CONCLUSIONS
  Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Miaofei
authors.initials: M
authors.lastname: Xu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qu
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Shoulin
authors.initials: S
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D059472:Exome; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009845:Oligospermia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide