LAUSR

Genome-wide association studies by the PRACTICAL consortium have identified and validated 147 single nucleotide polymorphisms (SNPs) associated with prostate cancer (PCa) risk (Schumacher et al., Nat Genet 2017). However, most of these genetic variants are in noncoding regions, which poses a challenge for understanding the molecular mechanisms underlying these risk loci. Herein we study both expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL) among these PCa risk loci to identify molecular alterations associated with these genetic variants. Data were available for a Fred Hutchinson (FH)-based cohort of patients diagnosed with localized stage PCa, including SNP genotypes (Infinium iCOGS and OncoArray-500K BeadChips) from the PRACTICAL consortium and genome-wide DNA methylation (Infinium Human Methylation450 BeadChip) and gene expression (HumanHT-12 v4 BeadChip) profiling of primary tumor tissues obtained at radical prostatectomy. Missing genotypes were imputed using the October 2014 (Phase 3) release of the 1KGP data as the reference panel. These data were used to identify eQTL (N=355) and mQTL (N=377) in cis-acting associations where the transcripts or CpG sites are located within 2Mb (±1Mb) of the genetic variants. The Matrix eQTL software was used to conduct eQTL and mQTL analyses. In total, 4,300 SNP-transcript pairs and 104,600 SNP-CpG pairs were tested for eQTL and mQTL, respectively, among which we identified 64 eQTL-transcript pairs (37 PCa risk loci and transcripts in 54 genes) and 1,405 mQTL-CpG pairs (116 PCa risk loci and CpGs in 321 genes), after correction for multiple testing (FDR Citation Format: Xiaoyu Wang, Anqi Cheng, the PRACTICAL Consortium, Janet L. Stanford, James Y. Dai. An eQTL and mQTL study of 147 genetic variants associated with prostate cancer susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1218.