An expanded variant list and assembly annotation identifies multiple novel coding and noncoding genes for prostate...

Area of Science:

• Genetics
• Oncology
• Bioinformatics

Background:

• Prostate cancer (PrCa) exhibits high heritability, with numerous risk variants identified but few associated genes known.
• Expression quantitative trait loci (eQTL) studies are crucial for linking genetic variants to gene expression and understanding their role in disease risk.

Purpose of the Study:

• To perform eQTL analysis on normal prostate epithelium samples and known PrCa-risk variants.
• To identify genes regulated by PrCa-risk variants and elucidate their potential role in prostate cancer development.

Main Methods:

• Utilized RNA sequencing transcriptome data from 471 normal prostate epithelium samples.
• Analyzed 249 PrCa-risk variants across 196 risk loci using ENSEMBL gene definition and genome-wide variant data.
• Performed eQTL analysis to associate variants with gene expression levels.

Main Results:

• Identified 213 genes associated with known PrCa-risk variants, including protein-coding genes, lncRNAs, and other non-coding RNAs.
• Detected eQTL signals in 102 (52%) of the 196 tested loci.
• Found 52 (51%) of the eQTL signals were Group 1, indicating high linkage disequilibrium (LD) with PrCa-risk variants.

Conclusions:

• The study successfully linked numerous PrCa-risk variants to specific genes through eQTL analysis.
• Findings provide insights into the regulatory mechanisms by which genetic variants influence prostate cancer risk.
• The use of ENSEMBL gene definition identified more associated genes compared to previous RefSeq-based analyses.