title: Systematic enrichment analysis of potentially functional regions for 103 prostate cancer risk-associated loci.
abstract: BACKGROUND
  More than 100 prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) have been identified by genome wide association studies (GWAS). However, the molecular mechanisms are unclear for most of these SNPs.
  
  
  METHODS
  All reported PCa risk-associated SNPs reaching the genome-wide significance level of P < 1 × 10(-7) (index SNPs), as well as SNPs in linkage disequilibrium (LD, r(2) ≥ 0.5) with them were cataloged. Genomic regions with potentially functional impact were also identified, including UCSC annotated coding regions (exon and snoRNA/miRNA) and regulatory regions, as well as binding regions for transcription factors (TFs), histone modifications (HMs), DNase I hypersensitivity (DHSs), and RNA Polymerase IIA (POLR2A) defined by ChIP-Seq in prostate cell lines and tissues. Enrichment analysis was performed to test whether PCa risk-associated SNPs are located in these functional regions more than expected.
  
  
  RESULTS
  A total of 103 PCa risk-associated index SNPs and 7,244 SNPs in LD with these index SNPs were cataloged. Genomic regions with potentially functional impact, grouped in 30 different categories of functionalities, were identified. Enrichment analysis indicated that genomic regions in the following 15 categories were enriched for the PCa risk-associated SNPs: exons, CpG regions, 6 TFs (AR, ERG, FOXA1, HOXB13, CTCF, and NR3C1), 5 HMs (H3K4me1, H3K4me2, H3K4me3, H3K27AC, and H3T11P), DHSs and POLR2A. In contrast, significantly fewer PCa risk SNPs were mapped to binding regions for H3K27me3, a repressive chromatin marker.
  
  
  CONCLUSIONS
  The PCa risk-associated SNPs discovered to date may affect PCa risk through multiple different mechanisms, especially by affecting binding regions of TFs/HMs.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.|Center for Genomic Translational Medicine and Prevention, Fudan School of Public Health, Fudan University, Shanghai, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Program for Personalized Cancer Care and Department of Surgery, North Shore University Health System, Evanston, Illinois.
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.|Program for Personalized Cancer Care and Department of Surgery, North Shore University Health System, Evanston, Illinois.
authors.forename: Deke
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.|Program for Personalized Cancer Care and Department of Surgery, North Shore University Health System, Evanston, Illinois.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Gong-Hong
authors.initials: GH
authors.lastname: Wei
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: William B
authors.initials: WB
authors.lastname: Issacs
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.
authors.forename: Junjie
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China.|Center for Cancer Genomics, Wake Forest University School of Medicine, Winston Salem, North Carolina.|Center for Genomic Translational Medicine and Prevention, Fudan School of Public Health, Fudan University, Shanghai, P.R. China.|Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, P.R. China.|Program for Personalized Cancer Care and Department of Surgery, North Shore University Health System, Evanston, Illinois.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors
keywords: genome-wide association study; histone modifications; transcription factor binding regions