Genomic Regions Associated with Bovine Respiratory Disease in Pacific Northwest Holstein Cattle

Authors: ALLISON, HERRICK - Washington State University; JENNIFER, KISER - Washington State University; White, Stephen; HOLLY, NEIBERGS - Washington State University

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/14/2025
Publication Date: 7/31/2025
Citation: Allison, H.L., Jennifer, K.N., White, S.N., Holly, N.L. 2025. Genomic Regions Associated with Bovine Respiratory Disease in Pacific Northwest Holstein Cattle. Frontiers in Genetics. 12:1637087. https://doi.org/10.3389/fvets.2025.1637087.
DOI: https://doi.org/10.3389/fvets.2025.1637087

Interpretive Summary: Introduction: Bovine respiratory disease (BRD) is the leading natural cause of death in cattle. It is a multifactorial disease comprised of a complex of bacterial and viral pathogens. To aid in the reduction of BRD morbidity and mortality and the selection of cattle with reduced susceptibility, the objectives of this study were to identify genes and loci associated with BRD in pre-weaned and post-weaned Holstein calves. Methods: From a single dairy, there were 518 pre-weaned (0-60 days old) and 2,001 post-weaned (61-421 days old) Holstein heifers that were treated for BRD and served as cases. All pre-weaned 3,655 healthy controls calves remained in the herd for a minimum of 60 days, and 3,210 healthy post-weaned controls calves remained in the herd for a minimum of 421 days to qualify for the study. Results: There were 4 additive, 6 dominant and 3 recessive loci associated (p < 5 x 10-7) with BRD in pre-weaned calves and 22 additive, 17 dominant and 13 recessive loci associated with BRD in post-weaned calves. In pre-weaned calves, SNPs associated with BRD were within 26 positional candidate genes and in 56 positional candidate genes in post-weaned calves. The positional candidate genes, EBF1 and SPAG16, and the leading-edge analysis gene COL4A3BP were shared between the pre- and post-weaned calves. NEU2 and SENP7 were shared as positional candidate and leading-edge analysis genes in pre-weaned calves, and post-weaned calves, respectively. NEU2 encodes neuraminidase 2, which might function to deplete entry receptors for BRD pathogen influenza D virus. The identification of genes and loci associated with BRD in different ages of dairy calves provides a better understanding of the disease process and facilitates selection for animals more resistant to this complex disease.

Technical Abstract: Introduction: Bovine respiratory disease (BRD) is the leading natural cause of death in cattle. It is a multifactorial disease comprised of a complex of bacterial and viral pathogens. To aid in the reduction of BRD morbidity and mortality and the selection of cattle with reduced susceptibility, the objectives of this study were to identify loci, gene sets, positional candidate and leading-edge genes associated with or enriched for BRD in pre-weaned and post-weaned Holstein calves. Methods: From a single dairy, there were 518 pre-weaned (0-60 days old) and 2,001 post-weaned (61-421 days old) Holstein heifers that were treated for BRD and served as cases. All pre-weaned 3,655 healthy controls calves remained in the herd for a minimum of 60 days, and 3,210 healthy post-weaned controls calves remained in the herd for a minimum of 421 days to qualify for the study. Loci associated (uncorrected p < 5 x 10-7) with BRD were identified using EMMAX with additive, dominant and recessive inheritance models. Heritability was estimated using GBLUP. For loci associated with BRD, positional candidate genes were identified within a haplotype of an associated SNP. A GSEA-SNP was performed to identify gene sets (NES = 3) and leading-edge genes enriched for BRD. Results: There were 4 additive, 6 dominant and 3 recessive loci associated (p < 5 x 10-7) with BRD in pre-weaned calves and 22 additive, 17 dominant and 13 recessive loci associated with BRD in post-weaned calves. In pre-weaned calves, SNPs associated with BRD were within 26 positional candidate genes and in 56 positional candidate genes in post-weaned calves. Heritability was estimated as 0.16 ± 0.02 for both pre-weaned and post-weaned heifers. One gene set with 86 leading edge genes was enriched (NES = 3) for the pre-weaned calves while 7 gene sets with 162 unique leading-edge genes were enriched (NES = 3) in the post-weaned calves. The positional candidate genes, EBF1 and SPAG16, and the leading-edge gene COL4A3BP were shared between the pre- and post-weaned calves. NEU2 and SENP7 were shared as positional candidate and leading-edge genes in pre-weaned calves, and post-weaned calves, respectively. NEU2 encodes neuraminidase 2, which might function to deplete sialic acid entry receptors for BRD pathogen influenza D virus. The identification of loci, gene sets, positional candidate and leading-edge genes associated and enriched for BRD in different ages of dairy calves provides a better understanding of the disease process and facilitates selection for animals more resistant to this complex disease.