Multi-omics data integration towards sustainable bovine production, health and welfare: the case of painful foot lesions

Abstract Claw horn disruption lesions (CHDL) are painful non-infectious foot lesions of significant animal welfare and socioeconomic importance to the dairy industry. Lameness caused by CHDL is the main cause of involuntary culling, considerably reduces milk production, constitutes a major animal welfare concern and impacts directly on sustainability through increased costs, veterinary intervention and raising replacement cattle with environmental implications. As a complex heritable disease, better understanding of the genomic architecture of CHDL pathogenesis and development is essential for facilitating genetic improvement of hoof health. We have collected detailed longitudinal phenotypic, genetic data and metadata from 2,300 dairy cattle and performed an in-depth genetic characterisation integrating multi-omics data including: genome-wide association studies (GWAS), whole genome sequencing (WGS), mRNA-sequencing, lncRNA-sequencing, expression quantitative trait loci (eQTL), reduced representation bisulfide sequencing (RRBS) in foot tissue and peripheral blood lymphocytes. According to our results, pathways related to complement cascade, inflammation, neuronal signalling (specifically pain perception) and bone and cartilage development, play a key role in CHDL resistance. These findings highlight novel genetic targets for precise breeding strategies to reduce CHDL prevalence. Implementation could improve animal welfare, decrease involuntary culling, and enhance dairy sector sustainability by enabling smaller herds with reduced methane emissions and resource use.