Genome-Wide Association Studies Reveal Susceptibility Loci for Digital Dermatitis in Holstein Cattle

SIMPLE SUMMARY: Foot warts (FW), a leading cause of foot problems in dairy cattle, is a welfare concern and causes financial losses due to treatment and reduced milk production. Foot warts, or the technically correct term of digital dermatitis, result from a bacterial infection followed by delayed healing due to both genetic and environmental factors. Dairy farmers are already combatting FW through environmental control, but they do not have genetic selection tools because the genetics influencing FW susceptibility are largely unknown. We sought to identify the genetics associated with FW which can be incorporated into genetic selection tools. Farmers can then use these genetic selection tools to breed cows that are less susceptible to FW. We identified promising genes that play a role in the immune response and wound healing—immune functions that, if impaired, could increase a cow’s susceptibility to FW. Though these genes were promising, their associated genetic markers had very little influence on FW susceptibility when compared to environmental management. Thus, the findings imply that the best approach for reducing FW prevalence is likely through combining a genetics approach with environmental management. ABSTRACT: Digital dermatitis (DD) causes lameness in dairy cattle. To detect the quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high-density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record) and recurrent (cases with ≥2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified the top SNPs, which were used as predictors in Bayesian regression models to assess the SNP predictive value. The LMM and RF analyses identified QTL regions containing candidate genes on Bos taurus autosome (BTA) 2 for the binary and recurrent phenotypes and BTA7 and 20 for the quantitative phenotype that related to epidermal integrity, immune function, and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with a high predictive value.