Post genome-wide association studies functional characterization of prostate cancer risk loci

摘要: Over the last decade, genome-wide association studies (GWAS) have discovered many risk associated single nucleotide polymorphisms (SNPs) of prostate cancer (PCa). However, majority PCa SNPs, including those in linkage disequilibrium (LD) blocks, are generally not located protein coding regions. The systematical investigation functional roles these especially non-coding becomes very necessary and helpful to understanding molecular mechanism PCa. In this work, we proposed a comprehensive framework at network level integrate SNP annotation, target gene assignment, ontology (GO) classification, pathway enrichment analysis regulatory reconstruction illustrate functions SNPs. By LD expansion, first identified 1828 SNPs using 49 reported GWAS as start. We carefully annotated via either UCSC known genes, regulation elements, or expression Quantitative Trait Loci (eQTL) data. As result, found 1154 were functionally obtained 205 unique genes for further analysis. enriched GO biological processes pathways mainly related cell death, apoptosis, proliferation, metabolic process, which been proved essential development. constructed specific transcription networks, finding several important genetic regulators PCa, such IGF-1/IGF-2 receptors, SP1, CREB1, androgen receptor (AR). A was integrative systematic can provide information function will facilitate discovery novel candidate biomarkers diagnosis prognosis