Shared Genetics of Kidney Function Traits and Bladder Cancer: A Genome-Wide Cross-Trait Analysis

Area of Science:

• Genetics
• Genomics
• Cancer Research

Background:

• Clinical and epidemiological data suggest a link between kidney dysfunction and bladder cancer (BC).
• The shared genetic etiology underlying this comorbidity remains largely unknown.
• Investigating shared genetics is crucial for understanding the complex relationship between kidney function and BC.

Purpose of the Study:

• To investigate the shared genetic architecture between kidney dysfunction and bladder cancer.
• To identify overlapping genetic loci and infer causal relationships.
• To elucidate the biological functions and molecular mechanisms connecting these conditions.

Main Methods:

• Genome-wide cross-trait analysis using summary statistics from large-scale GWAS in European populations.
• Evaluated genetic correlation using LD score regression (LDSC).
• Employed multi-trait analysis of GWAS (MTAG), colocalization, transcriptome-wide association analysis (TWAS), and bidirectional Mendelian randomization (MR) for causal inference.

Main Results:

• Positive genome-wide correlations were observed between blood urea nitrogen (BUN) and urate levels with BC.
• Identified 157 significant overlapping genetic loci between five kidney function traits and BC.
• Prioritized PSCA as a key shared gene; MR suggested a potential causal effect of BUN on BC.

Conclusions:

• Demonstrated a shared genetic basis between kidney function and BC.
• Provided novel insights into the biological functions and molecular mechanisms underlying these complex traits.
• Findings support further research into the genetic links between renal health and bladder cancer risk.