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

• Published in: Carcinogenesis (New York) 2011-11, Vol.32 (11), p.1655-1659
• Main Authors: Jin, Guangfu, Sun, Jielin, Isaacs, Sarah D., Wiley, Kathleen E., Kim, Seong-Tae, Chu, Lisa W., Zhang, Zheng, Zhao, Hui, Zheng, Siqun Lilly, Isaacs, William B., Xu, Jianfeng
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Meta-Analysis as Topic; Molecular Epidemiology; Nephrology. Urinary tract diseases; Phenotype; Polymorphism, Single Nucleotide - genetics; Prostatic Neoplasms - genetics; Risk Factors; RNA, Untranslated - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgr187

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.