title: Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk.
abstract: Long non-coding RNAs (lncRNAs), representing a large proportion of non-coding transcripts across the human genome, are evolutionally conserved and biologically functional. At least one-third of the phenotype-related loci identified by genome-wide association studies (GWAS) are mapped to non-coding intervals. However, the relationships between phenotype-related loci and lncRNAs are largely unknown. Utilizing the 1000 Genomes data, we compared single-nucleotide polymorphisms (SNPs) within the sequences of lncRNA and protein-coding genes as defined in the Ensembl database. We further annotated the phenotype-related SNPs reported by GWAS at lncRNA intervals. Because prostate cancer (PCa) risk-related loci were enriched in lncRNAs, we then performed meta-analysis of two existing GWAS for discovery and an additional sample set for replication, revealing PCa risk-related loci at lncRNA regions. The SNP density in regions of lncRNA was similar to that in protein-coding regions, but they were less polymorphic than surrounding regions. Among the 1998 phenotype-related SNPs identified by GWAS, 52 loci were located directly in lncRNA intervals with a 1.5-fold enrichment compared with the entire genome. More than a 5-fold enrichment was observed for eight PCa risk-related loci in lncRNA genes. We also identified a new PCa risk-related SNP rs3787016 in an lncRNA region at 19q13 (per allele odds ratio = 1.19; 95% confidence interval: 1.11-1.27) with P value of 7.22 × 10(-7). lncRNAs may be important for interpreting and mining GWAS data. However, the catalog of lncRNAs needs to be better characterized in order to fully evaluate the relationship of phenotype-related loci with lncRNAs.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Siqun Lilly
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
mesh_terms: D000368:Aged; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D012307:Risk Factors
chemical_list: D022661:RNA, Untranslated