Genetic parameters and genome-wide association study of digital cushion thickness in Holstein cows

The digital cushion is linked to the development of claw horn lesions (CHL) in dairy cattle. The objectives of this study were to (1) estimate genetic parameters for digital cushion thickness (DCT), (2) estimate the genetic correlation between DCT and CHL, and (3) identify candidate genes associated with DCT. A cohort of 2,352 Holstein dairy cows were prospectively enrolled on 4 farms and assessed at 4 time points: before calving, immediately after calving, in early lactation, and in late lactation. At each time point, CHL was recorded by veterinary surgeons, and ultrasonographic images of the digital cushion were stored and retrospectively measured at 2 anatomical locations. Animals were genotyped and pedigree details extracted from the national database. Genetic parameters were estimated following a single-step approach implemented in AIREMLF90. Four traits were analyzed: the 2 DCT measurements, sole lesions (sole hemorrhage and sole ulcers), and white line lesions. All traits were analyzed with univariate linear mixed models; bivariate models were fit to estimate the genetic correlation between traits within and between time points. Single-marker and window-based genome-wide association analyses of DCT traits were conducted at each time point; candidate genes were mapped near (<0.2 Mb) or within the genomic markers or windows with the largest effects. Heritability estimates of DCT ranged from 0.14 to 0.44 depending on the location of DCT measurement and assessment time point. The genetic correlation between DCT and sole lesions was generally negative, notably between DCT immediately after calving and sole lesions in early or late lactation, and between DCT in early or late lactation and sole lesion severity in early or late lactation. Digital cushion thickness was not genetically correlated with white line lesions. A polygenic background to DCT was found; genes associated with inflammation, fat metabolism, and bone development were mapped near or within the top markers and windows. The moderate heritability of DCT provides an opportunity to use selective breeding to change DCT in a population. The negative genetic correlation between DCT and sole lesions at different stages of production lends support to current hypotheses of sole lesion pathogenesis. Highlighted candidate genes provide information regarding the complex genetic background of DCT in Holstein cows, but further studies are needed to explore and corroborate these findings.