title: Functional annotation of risk loci identified through genome-wide association studies for prostate cancer.
abstract: BACKGROUND
  The majority of established prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies do not fall into protein coding regions. Therefore, the mechanisms by which these SNPs affect PCa risk remain unclear. Here, we used a series of bioinformatic tools and databases to provide possible molecular insights into the actions of risk SNPs.
  
  
  RESULTS
  We performed a comprehensive assessment of the potential functional impact of 33 SNPs that were identified and confirmed as associated with PCa risk in previous studies. For these 33 SNPs and additional SNPs in linkage disequilibrium (LD) (r(2)  ≥ 0.5), we first mapped them to genomic functional annotation databases, including the encyclopedia of DNA elements (ENCODE), 11 genomic regulatory elements databases defined by the University of California Santa Cruz (UCSC) table browser, and androgen receptor (AR)-binding sites defined by a ChIP-chip technique. Enrichment analysis was then carried out to assess whether the risk SNP blocks were enriched in the various annotation sets. Risk SNP blocks were significantly enriched over that expected by chance in two annotation sets, including AR-binding sites (P = 0.003), and FoxA1-binding sites (P = 0.05). About one-third of the 33 risk SNP blocks are located within AR-binding regions.
  
  
  CONCLUSIONS
  The significant enrichment of risk SNPs in AR-binding sites may suggest a potential molecular mechanism for these SNPs in PCa initiation, and provide guidance for future functional studies.
authors.affiliation: James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, China; T-Life Research Center Fudan University, Shanghai, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Lu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.forename: S Lily
authors.initials: SL
authors.lastname: Zheng
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
mesh_terms: D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen