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

Claw horn disruption lesions (CHDL) are painful non-infectious foot lesions with significant animal welfare and socioeconomic impacts on 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 the sustainability of the sector through increased costs, veterinary intervention and raising replacement cattle with environmental implications. As a complex heritable polygenic disease, better understanding of the genomic architecture of CHDL pathogenesis and development is essential for facilitating genetic improvement of hoof health. Here we have performed in-depth genetic characterisation of ~ 3,000 cattle integrating multi-omic analyses: genome-wide association studies, whole genome sequencing, mRNA-sequencing, lncRNA-sequencing, expression quantitative trait loci analyses, reduced representation bisulfide sequencing, and multi-omics factor analysis (MOFA) in foot tissue and peripheral blood lymphocytes. Identified genetic variants and underlying pathways related to resistance to CHDL development elucidated new findings on underlying mechanisms including: complement cascade, inflammation, neuronal signalling (specifically perception of pain) and bone and cartilage development. This novel data could be applied to sustainably improve animal health and welfare as well as support the cattle sector.