Genome-wide association study identifies loci influencing natural antibody titers in milk of Dutch Holstein-Friesian cattle

Natural antibodies (NAb) are produced without any antigenic stimulation as a part of the innate immune system and provide a first line of defense against pathogens. Hence, they may be a useful trait when estimating an animal's potential immune competence and in selection for disease resistance. The aim of this study was to identify genomic regions associated with different NAb traits in milk and potentially describe candidate genes. Milk samples from 1,695 first-lactation Holstein Friesian cows with titer measurements for keyhole limpet hemocyanin, lipopolysaccharide, lipoteichoic acid, and peptidoglycan-binding total NAb and isotypes IgG₁, IgM, and IgA were used. Genome-wide association study analyses were performed using imputed 777K SNP genotypes, accounting for relationships using pedigree information. Functional enrichment analysis was performed on the significantly associated genomic regions to look for candidate genes. For IgM NAb, significant associations (false discovery rate <0.05) were found on Bos taurus autosome (BTA) 17, 18, and 21 with candidate genes related to immunoglobulin structure and early B cell development. For IgG₁, associations were found on BTA3, and we confirmed a quantitative trait loci on BTA21 previously reported for IgG NAb in serum. Our results provide new insights into the regulation of milk NAb that will help unravel the complex relationship between milk immunoglobulins and disease resistance in dairy cattle.