Abstract Background The yak is an important source of livelihood for the people living in the Qinghai-Tibet Plateau. Most genetics detection studies have focused on the comparison between different tissues of different breeds, both living in the Plateau and in the plains. The genetic background and complex regulatory relationship have frequently puzzled researchers. In this study, we divided a population of 10 yaks into two subgroups, namely Plateau (living in the Plateau) and Plain (living in the plains). Phenomic, genomic, and transcriptomic analyses were used to reveal the molecular genetic type in the body weight, slaughter, and beef quality of yaks. Results We found a significant difference (P <0.01) between the third (60 days), fourth (90 days), fifth (120 days), and sixth (150 days) weights of Plateau and plain subpopulations. The difference in body weight was due to differences in kidney weight, meat weight, fur weight, and head weight. However, the beef quality was not significantly different. We identified 540 Differentially Expressed Genes (DEGs). Using weighted gene co-expression network analysis (WGCNA), we have constructed a co-express network, and the modules were strongly related to traits. In the genome-wide association studies (GWAS), we detected significant 156, 52, 33, 15, and 3 signals in the meat weight, head weight, fur weight, liver weight, and the last body weight traits. Based on the epigenome-wide association studies (eWAS) results, we created a link relationship between the DEGs expression level and genotype. Conclusion In summary, our study demonstrated the effectiveness and representative of multidimensional data from a finite number of yak populations. The study highlights the underlying way, as well as a related network, to yield new information on genome genetics and pathogen-host interactions of both the living Plateau and plain yak populations.