In recent years, while monitoring commercial laying hens during the brooding period, we noticed that some chicks exhibited an abnormal lameness phenomenon. Systematic tests were carried out for pathogens including, but not limited to, common diseases such as viral arthritis, mycoplasma synoviae, Marek's disease and encephalomyelitis. However, the absence of these pathogens in these chicks rules out these common diseases as a direct cause of limping and points to genetic factors. Leg disorders in laying hens pose significant welfare challenges and result in considerable economic losses within the poultry industry. To address this issue, we conducted a comprehensive genomic and transcriptomic analysis to uncover the genetic basis of leg diseases in laying hens. Our study involved 74 laying hens with leg diseases and 60 healthy controls from three different strains. Radiographic identification and resequencing were performed to analyze genetic loci and candidate genes. Transcriptomic analysis was also conducted on cartilage tissues from both groups. Four potential single nucleotide polymorphism (SNP) loci located on chromosomes 4 and 33 were identified through genome-wide association studies (GWAS). Notably, the functional candidate gene SORCS2 has been particularly implicated in the pathogenesis of leg disease. A total of 1,515 differentially expressed genes (DEGs) were identified through transcriptomic analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant enrichment in pathways such as cytoskeletal protein binding, cell cycle regulation, and muscle cell cytoskeleton organization. Notably, the calcium signaling and the extracellular matrix (ECM)-receptor interaction pathways were associated with the development of leg diseases. The integration of genomic and transcriptomic data identified key genetic loci and candidate genes associated with leg health, providing a genetic foundation for improving disease resistance in laying hens. Our findings offer valuable insights for the development of selective breeding strategies to reduce the incidence of leg disorders in laying hens, thereby enhancing their welfare and productivity.