Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk

Guangfu Jin, Jielin Sun, Sarah D. Isaacs, Kathleen E. Wiley, Seong Tae Kim, Lisa W. Chu, Zheng Zhang, Hui Zhao, Siqun Lilly Zheng, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1655-1659
Number of pages5
JournalCarcinogenesis
Volume32
Issue number11
DOIs
StatePublished - Nov 2011

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Jin, G., Sun, J., Isaacs, S. D., Wiley, K. E., Kim, S. T., Chu, L. W., Zhang, Z., Zhao, H., Zheng, S. L., Isaacs, W. B., & Xu, J. (2011). Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk. Carcinogenesis, 32(11), 1655-1659. https://doi.org/10.1093/carcin/bgr187