A Multidisciplinary Approach to Genome Wide Association Analysis Reveals Susceptibility Loci for Bovine Respiratory Disease Complex

Bovine respiratory disease complex (BRDC) is an infectious disease that occurs when combinations of bacterial and viral pathogens infect cattle during times of stress. It is estimated that BRDC is responsible for over $800 million in losses each year in dairy and beef cattle (Chirase & Greene 2001). The aim of the BRDC consortium is to reduce the prevalence of respiratory disease through selection of cattle less susceptible to BRDC. To identify BRDC susceptible cattle, pre-weaned Holstein calves from California (CA) (n=2015 ) and New Mexico (NM) (n=763) were identified as cases (McGuirk score ≥5) or controls (McGuirk score <5), swabbed for viral and bacterial pathogens, and their DNA extracted for genotyping with the Illumina BovineHD BeadChip. GWAS was performed for the case-control phenotype for CA, NM and CA & NM using EMMAX-GRM, GBLUP, PLINK and full versus reduced model logistic (FvR) regression within SNP & Variation Suite 7. Heritability was estimated; haplotype analysis was performed with Haploview, and used for mapping SNPs to genes for the gene set enrichment analysis. Heritability estimates for BRDC susceptibility were 19-21% for NM and CA as individual populations and 13% when combined. Associations of several single SNPs and regions were shared across all four analyses. Several gene sets were identified with normalized enrichment scores (NES) >3.0 in CA, NM and CA & NM analyses. These results support the genetic control of BRDC susceptibility and that selection against BRDC is a feasible approach to reduce respiratory disease prevalence.