Transcriptome-wide association study of prostate cancer in the Chinese population

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Prostate cancer (PCa) is a common male malignancy with significant genetic links.
• Genome-wide association studies (GWAS) have identified many PCa risk loci, but causal genes remain unclear.

Purpose of the Study:

• To conduct the first transcriptome-wide association study (TWAS) for PCa in the Chinese population.
• To systematically identify putative causal target genes contributing to PCa development.

Main Methods:

• Utilized single-tissue and cross-tissue TWAS approaches on 5048 participants (2550 PCa cases, 2498 controls).
• Employed Mendelian randomization for causal inference and analyzed differential gene expression and methylation.
• Assessed prognostic significance through survival analysis.

Main Results:

• Identified 290 putative causal genes for PCa across two cohorts.
• Meta-analysis revealed 23 significant genes via single-tissue TWAS and 9 additional genes via cross-tissue TWAS.
• GRAMD2 was consistently associated; TRAPPC6B and PNPLA6 showed causal roles in PCa etiology.

Conclusions:

• This comprehensive TWAS in the Chinese population identified numerous PCa-associated genes.
• Findings improve understanding of PCa pathogenesis and offer potential molecular targets and biomarkers.