Longitudinal Phenotypes Improve Genotype Association for Hyperketonemia in Dairy Cattle

SIMPLE SUMMARY: Dairy cows have differing success in supporting their physiological functions while in energy deficit right after calving. Identification of genomic regions associated with different concentrations of non–esterified fatty acids and β–hydroxybutyrate in early postpartum Holstein cows provide insight into an animal’s genetic susceptibility to these conditions. Longitudinal phenotypes may provide a different perspective than cross-sectional phenotype variation and their association with genotypes in the study of complex metabolic diseases in dairy cows. This might allow us to reinforce preventative measures that decrease the incidence of hyperketonemia and improve genetic selection criteria. ABSTRACT: The objective of our study was to identify genomic regions associated with varying concentrations of non-esterified fatty acid (NEFA), β-hydroxybutyrate (BHB), and the development of hyperketonemia (HYK) in longitudinally sampled Holstein dairy cows. Our study population consisted of 147 multiparous cows intensively characterized by serial NEFA and BHB concentrations. To identify individuals with contrasting combinations in longitudinal BHB and NEFA concentrations, phenotypes were established using incremental area under the curve (AUC) and categorized as follows: Group (1) high NEFA and high BHB, group (2) low NEFA and high BHB), group (3) low NEFA and low BHB, and group (4) high NEFA and low BHB. Cows were genotyped on the Illumina Bovine High-density (777 K) beadchip. Genome-wide association studies using mixed linear models with the least-related animals were performed to establish a genetic association with HYK, BHB-AUC, NEFA-AUC, and the comparisons of the 4 AUC phenotypic groups using Golden Helix software. Nine single-nucleotide polymorphisms were associated with high longitudinal concentrations of BHB and further investigated. Five candidate genes related to energy metabolism and homeostasis were identified. These results provide biological insight and help identify susceptible animals thus improving genetic selection criteria thereby decreasing the incidence of HYK.