Genetic and non-genetic factors distinctly shape the variation of the immune response in cattle

Increasing agricultural production while reducing the reliance on synthetic inputs such as antibiotics is an important challenge. For cattle breeding, this implies better understanding the genetics underlying meat production and the immune response. Here, we use systems immunology to investigate the genetic and environmental drivers of immune variation in Belgian White Blue male cattle, a breed historically bred for meat production. While seasonality and other non-genetic factors account for much of the immune variation observed, genome-wide association studies identify loci with major effects on specific immunophenotypes. Genetics also emerges as the primary driver of cytokine production. Finally, we develop a predictive model linking genetic data to cytokine responses. Our findings support the selection of cattle with improved immunity and advance our understanding of mammalian immune variation.