Shared genetic architecture of Genitourinary Cancer and Heart Failure

Abstract

Background Epidemiological and clinical investigations have established a robust correlation between Cancer and Heart Failure, with patients afflicted by either condition being at an elevated risk of developing the other.But the existence of a shared genetic etiology remains elusive.The objective was to ascertain the shared genetic between genitourinary cancer and heart failure. Methods Conducted a genetic association analysis between common genitourinary tumors and heart failure using genome-wide association study data. Identified the corresponding pleiotropic loci and genes through various statistical methods, and performed tissue and immune cell enrichment analyses for these pleiotropic genes. Furthermore, evaluated the causal relationship between them using two-sample Mendelian randomization. Results Identified significant shared genetic bases among Bladder, Endometrial, Kidney cancer and Heart failure. Specifically, discovered 5 shared genetic loci: rs10757277, rs1537372, rs543968, rs653178 and rs56094641. These loci are associated with related genes such as CDKN2B-AS1,ANRIL, ABO, ATXN2, and FTO. Furthermore, the genes CADM2,CELSR2 were identifiedgene. Pleiotropy was found to be significantly enriched in various tissues including prostate, cervix, testis intestinal-terminalileum et cetera. Additionally, a diverse range of immune cells were specifically enriched in these two types of diseases. Mendelian randomization analysis provided suggestive evidence for these findings. Conclusions Bladder, Endometrial,Kidney cancer and Heart failure have underlying mechanisms of shared genetic. Our results also suggest that the immune system plays an important role in these two types of diseases.These findings provide support for a shared genetic basis underlying both disease types and offer novel evidence for targeted therapeutic interventions against them.