We conducted congenic mapping experiments for radiation-induced cardiotoxicity (RIC) in rats. We identified an ∼67 MB region on chromosome 3 of the R. norvegicus genome containing 869 coding genes. We hypothesized that human orthologs of the genes within this region function in human phenotypes of cardiac dysfunction. Here, we aimed to determine the enrichment of variants regulating these human orthologs in genome-wide association study (GWAS) of heart failure (HF) and to identify candidate genes for future studies of RIC. We performed ortholog mapping using Ensemble (v. 99). We investigated whether single nucleotide polymorphisms (SNPs) regulating the expression of these genes were associated with HF. We utilized the summary statistics from a GWAS of HF performed in the UK Biobank. We extracted regulatory expression quantitative trait loci (eQTLs) from GTEx in tissues with hypothesized relevance: coronary artery, cultured fibroblasts, left ventricle, and whole blood. We assessed for enrichment using an empirical Brown’s combined p-value method for dependent data, using 1000 Genomes v3 to generate a linkage disequilibrium correlation matrix. We found 633 human orthologs of the 869 RIC congenic region coding genes. There was significant enrichment of eQTLs regulating these orthologs in the human GWAS of HF in whole blood (p = 0.003), left ventricle (p = 0.04), and cultured fibroblast (p = 0.00006), but not the coronary artery (p = 0.28). In fibroblast tissue, 19 genes were implicated in HF GWAS with p<0.005 including: PROCR, involved in coagulation and defected in thrombophilia disorders; KCNIP3, a voltage-gated potassium channel affecting cardiac conductivity and membrane excitability; and TMEM87B, implicated in congenital heart defects and restrictive cardiomyopathy. Other genes include UQCC1, LZTS3, ITPA, CPNE1, RPL13, XRN2, MAP1LC3A, TM9SF4, SIRPB1, and SIRPA. Genes uniquely discovered in whole blood tissue were: KIZ, TRCP4AP, GATM, EIF6, OSER1, and DDRGK1. Genes uniquely discovered in the left ventricle were: NDUFAF1, DUOXA1, DUOX1, SHF, FERMT1, TOX2. We found a statistically significant enrichment of regulatory variants in rat-discovered RIC genes in human GWAS of HF. This implies a shared genetic architecture of rat RIC and human HF. Our analysis may suggest a chronic remodeling and fibrosis phenotype underlying both HF and RIC. This analysis identified a number of genes to prioritize for future investigations. Our approach integrates an experimental animal model with human in silico analyses, providing a novel translational approach for discovery and cross-validation of genes identified in pre-clinical studies. Future studies will further map the congenic region and test candidate genes experimentally and identify genetic variants that influence RIC.