Abstract 4633: Evidence that long non-coding RNA variants associate with epithelial ovarian cancer risk

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.4633-4633
• Main Authors: Sellers, Thomas A., Reid, Brett M., Chen, Y. Ann, Lin, Hui-Yi, Richards, Edward, Teer, Jamie, Monteiro, Alvaro, Chen, Zhihua, Berchuck, Andrew, Chenevix-Trench, Georgia, Doherty, Jennifer, Goode, Ellen, Iverson, Edwin, Pearce, Leigh, Pharoah, Paul, Phelan, Catherine, Ramus, Susan, Rossing, Mary Anne, Schildkraut, Joellen, Cheng, Jin, Gayther, Simon, Permuth-Wey, Jennifer
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-4633

Background: Genome wide association studies (GWAS) have identified 20 loci associated with epithelial ovarian cancer (EOC) risk. Additional EOC risk loci await identification, and biological approaches may represent a useful strategy for overcoming sample size limitations. The ENCODE project recently concluded that only ∼1.2% of the genome encodes proteins, but at least 20% exhibits biological function and over 80% exhibits biochemical indices of function. Post-GWAS follow-up studies have firmly established that some associations are due to inter-individual differences in non-coding RNAs (ncRNAs). To estimate the magnitude of impact of variants in long non-coding RNAs (lncRNAs), we assessed enrichment of EOC-associated SNPs in lncRNA regions by comparing the density of EOC-associated loci between lncRNA regions, non-lncRNA regions, and the whole genome. Methods: The study population included ∼18,000 invasive EOC cases and 34,000 healthy controls of European ancestry from the Ovarian Cancer Association Consortium with GWAS data imputed to 1000 Genomes Project (1KGP) density. Density was compared with two measures: average chromosome length required for one EOC-associated SNP (kb/locus) and average number of tested SNPs containing one EOC-associated SNP (SNPs/locus). Coordinates and annotation for 13,870 lncRNA genes were downloaded from the publicly available GENCODE (v19) database and were used to annotate SNPs from the 1KGP imputed GWAS data, yielding 13,192 lncRNA genes with biallelic variants imputed at rsquare ≥0.25. A SNP was considered EOC-associated if it reached a significance level of P