Epizootic hemorrhagic disease (EHD) is a noncontagious viral infection that can cause important economic losses on dairy farms. This study aimed to identify epidemiological and genetic factors influencing the susceptibility and severity of EHD in Holstein dairy cattle during the 2023 outbreak in Spain. Data from 2,852 animals in 7 affected farms from 5 Spanish provinces were used. Symptoms were categorized in 5 categories: no symptoms, mild symptoms, severe symptoms and recovery, severe symptoms with aftereffects (sequelae), and severe symptoms followed by death. All animals were genotyped using the Illumina EuroG MD SNP array, and imputation to whole-genome sequencing was carried out using the 1,000 bull genomes dataset as a reference. Risk factors for EHD were explored using linear mixed effects models, as well as the loss of milk yield and culling risk probability due to severe EHD. In all, ∼66% of animals showed EHD virus antibodies, although only 25% of the sample in this study showed severe symptoms, and the death rate was 2% to 3%. Results indicated that age was the main risk factor for severe EHD, with older cows showing greater susceptibility. Production losses were significant in cows with moderate to severe symptoms, especially if the outbreak occurred mid lactation (up to -9 kg/d). Cows exhibiting severe symptoms demonstrated a markedly increased likelihood of being culled, with an odds ratio of 10.86 (95% CI: 6.08-19.41) for cows with severe symptoms. The genetic component of EHD was evaluated using REML procedures, and a GWAS was conducted to investigate genomic regions associated with the disease. An h2 of 0.08 was estimated, with some genes (AOC1, BST1, CD38, DPP6, DPYS, HOGA1, KMT2C, PIK2A, PIK3, and PI4K2A) associated with the disease showing involvement in immunity processes and the development of the pulmonary tree. This study underscores the genetic and epidemiological factors influencing EHD severity in dairy cattle, providing insights for managing future outbreaks and mitigating economic losses in affected regions.
