Genetic evaluations and genome-wide association studies for specific digital dermatitis diagnoses in dairy cows considering genotype x housing system interactions.

The present study aimed to use detailed phenotyping for the claw disorder digital dermatitis (DD) considering specific DD stages in 2 housing systems (conventional cubicle barns = CON and compost bedded pack barns = CBPB) to infer possible genotype x housing system interactions. The DD-stages included 2,980 observations for the 3 traits DD-sick, DD-acute and DD-chronic from 1,311 Holstein-Friesian and 399 Fleckvieh-Simmental cows. Selection of the 5 CBPB and 5 CON herds was based on a specific protocol to achieve a high level of herd similarity with regard to climate, feeding, milking system and location, but with pronounced housing system differences. Five other farms had "a mixed system" with 2 sub-herds, one representing CBPB and the other one CON. 899 cows (1530 observations) represented the CBPB system, and 811 cows (1450 observations) the CON system. The average disease prevalence was 20.47% for DD-sick, 13.88% for DD-acute and 5.34% for DD-chronic, with a higher prevalence in CON than in CBPB. After quality control of 50K genotypes, 38,495 SNPs from 926 cows remained for the ongoing genomic analyses. Genetic parameters for DD-sick, DD-acute and DD-chronic were estimated by applying single-step approaches for single-trait repeatability animal models considering the whole data set, and separately for the CON and CBPB subsets. Genetic correlations between same DD traits from different housing systems, and between DD-sick, DD-chronic and DD-acute, were estimated via bivariate animal models. Heritabilities based on the whole data set were 0.16 for DD-sick, 0.14 for DD-acute and 0.11 for DD-chronic. A slight increase of heritabilities and genetic variances was observed in CON compared with the "well-being" CBPB system, indicating a stronger genetic differentiation of diseases in a more challenging environment. Genetic correlations between same DD traits recorded in CON or CBPB were close to 0.80, disproving obvious genotype x housing system interactions. Genetic correlations among DD-sick, DD-acute and DD-chronic ranged from 0.58 to 0.81. SNP main effects and SNP x housing system interaction effects were estimated simultaneously via GWAS considering only the phenotypes from genotyped cows. Ongoing annotations of potential candidate genes focused on chromosomal segments 100 kb upstream and downstream from the significantly associated candidate SNP. GWAS for main effects indicated heterogeneous Manhattan plots for especially for DD-acute and DD-chronic, indicating particularities in disease pathogenesis. Nevertheless, a few shared annotated potential candidate genes, i.e., METTL25, AFF3, PRKG1 and TENM4 for DD-sick and DD-acute, were identified. These genes have direct or indirect effects on disease resistance or immunology. For the SNP x housing system interaction, the annotated genes ASXL1 and NOL4L on BTA 13 were relevant for DD-sick and DD-acute. Overall, the very similar genetic parameters for same traits in different environments and negligible genotype x housing system interactions indicate only minor effects on genetic evaluations for DD due to housing system particularities.