Genome-wide association studies of dairy cattle resistance to digital dermatitis recorded at four distinct lactation stages

Digital dermatitis (DD) is an endemic infectious hoof disease causing lameness in dairy cattle. The aim of the present study was to investigate the genetic profile of DD development using phenotypic and genotypic data on 2192 Holstein cows. The feet of each cow were clinically examined four times: pre-calving, shortly after calving, near peak of milk production, and in late lactation. Presence or absence of disease and proportion of healthy feet per cow constituted two DD phenotypes of study. For each phenotype and timepoint of clinical examination, we conducted single-step genome-wide association analyses to identify individual markers and genomic regions linked to DD. We focused on the ten 1-Mb windows that explained the largest proportion of the total genetic variance as well as windows that enclosed significant markers. Functional enrichment analysis was also applied to determine functional candidate genes for DD. Significant (P < 0.05) genomic heritability estimates were derived ranging from 0.21 to 0.25. Results revealed two markers on chromosomes 7 and 15 that were related to both disease phenotypes. Furthermore, we identified three genomic windows on chromosome 14 and one window on chromosome 7 each explaining more than 1% of the trait additive genetic variance. Functional enrichment analysis revealed multiple promising candidate genes implicated in hoof health, wound healing, and inflammatory skin diseases. Collectively, our results provide novel insights into the biological mechanism of host resistance to DD development in dairy cattle and support genomic selection towards improving foot health.