BackgroundA detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle. To prioritize the putative variants and genes, we ran a comprehensive genome-wide association studies (GWAS) analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle. Then, we applied expression quantitative trait loci (eQTL) mapping between the genotype variants and transcriptome of three tissues (longissimus dorsimuscle, backfat, and liver) in 120 cattle.ResultsWe identified 1,580 association signals for 21 beef agronomic traits using GWAS. We then illuminated 854,498cis-eQTLs for 6,017 genes and 46,970trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits. Thesecis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions. We observed an average of 43.5% improvement incis-eQTL discovery using multi-tissue eQTL mapping. Fine-mapping analysis revealed that 111, 192, and 194 variants were most likely to be causative to regulate gene expression in backfat, liver, and muscle, respectively. The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits. Via the colocalization and Mendelian randomization analyses, we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues, which included genes, such asNADSYN1,NDUFS3,LTFandKIFC2in liver,GRAMD1C, TMTC2andZNF613in backfat, as well asTIGAR, NDUFS3andL3HYPDHin muscle that could serve as the candidate genes for economic traits.ConclusionsThe extensive atlas of GWAS, eQTL, fine-mapping, and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40104-023-00876-7.