Exploring the shared genetic architecture between leukocyte telomere length and renal cell carcinoma: a cross-trait analysis

While epidemiological studies suggest an association between leukocyte telomere length (LTL) and renal cell carcinoma (RCC), the genetic basis underlying this relationship remains to be elucidated. We analyzed genome-wide association studies (GWAS) summary statistics from LTL (n = 472,174) and RCC(3,926 cases; 378,749 controls) cohorts. Comprehensive cross-trait analyses examined genetic correlations, causality, tissue enrichment, and pleiotropic loci. We identified significant genetic correlation between LTL and RCC (correlation = 0.0379, p = 0.0012) at both genome-wide and local levels. Meta-analysis revealed 25 novel pleiotropic loci, including a co-localized variant (rs1874330). Novel tissue-specific enrichment was observed in uterine and testicular tissues, with shared functional genes affecting both traits. Mendelian randomization provided evidence for a causal effect of LTL on RCC risk. This study establishes genetic links between LTL and RCC through shared architecture, tissue-specific patterns, and causal pathways, suggesting potential therapeutic targets and risk markers for future validation.