Exploring the Genetic Basis of Ketosis: Preliminary GWAS Findings on Beta-Hydroxybutyrate Levels in Holstein Cattle

Abstract

Ketosis is a metabolic condition characterized by a shift in energy metabolism, occurring when glucose availability is depleted and fat becomes the alternative primary energy source, resulting in the accumulation of ketone bodies. In dairy cattle, ketosis represents a significant challenge, adversely affecting both animal health and farm productivity. The genetic basis of ketosis in cattle has attracted increasing attention, with genome-wide association studies (GWAS) emerging as a crucial method for identifying relevant genetic factors. This study was aimed at investigating genome-wide regions associated with beta-hydroxybutyrate (BHB) concentrations in Holstein-Friesian cows' blood before calving in the United Kingdom. BHB measurement data from 253 previously genotyped cows were used in the analyses. The results revealed five significant SNPs on Chromosome 15 (BTA15) and one significant SNP on BTA5 (p < 1.60e - 6). Notably, the SNPs on BTA15 clustered within a genomic region enriched with genes implicated in lipid metabolism and energy balance, highlighting its potential role in ketosis susceptibility. These preliminary findings refine the genetic architecture of ketosis and offer new avenues for improving dairy cattle health and welfare through targeted genetic selection programs while highlighting the need for validation in larger and independent populations.

Keywords: QTL; dairy cattle ketosis; genome-wide association.

Figure 1

Multidimensional scaling (MDS) plot of 253 dairy cows based on genomic relationship matrix values. Each point represents an individual cow projected into two-dimensional space according to genetic similarity. Colors indicate farm of origin (red = Farm 1, green = Farm 2, and blue = Farm 3), shapes correspond to parity number, and point sizes reflect body condition score (BCS). The figure illustrates both genetic clustering and the distribution of animals across farms and physiological parameters.

Figure 2

Genome-wide Manhattan plot. The red line indicates the Bonferroni-corrected significance threshold of 1.60e − 6. The blue line indicates the Bonferroni-corrected suggestive threshold of 3.20e − 5.