Genome-wide association study for milk and blood indicators of hyperketonemia in Holstein dairy cattle

At the onset of lactation, specialized dairy cows commonly experience negative energy balance that often results into hyperketonemia (HYP) or even clinical ketosis. HYP diagnosis relies on the blood level of β-hydroxybutyrate (BHB), which is known to be the major and most stable ketone body in cows’ biological fluids, including milk. Recently, in fact, mid-infrared (MIR) spectroscopy prediction models for blood BHB concentration from milk spectra have been developed. Although characterized by moderate accuracy, MIR-predicted blood BHB is useful for selective breeding. We identified genomic regions associated with milk BHB and MIR-predicted blood BHB in Italian Holstein cattle to disclose potential overlaps and divergences. A single-step genome-wide association study was performed using the 2 phenotypes after log10-transformation collected in lactating cows within the 35th day in milk. The 8,277 cows with phenotypes available were genotyped with various SNP panels, so data were imputed up to approximately 70,000 SNP. After conventional quality controls, 63,408 markers located in autosomes (BTA) were left. The blood BHB significant regions were located in BTA 6, 11, 14, and 25, while those of milk BHB were in BTA 11. For blood BHB, the signals with the highest P-value were in the gene PAEP (BTA 11) and DGAT1 (BTA 14). For milk BHB, the most significant signal was found within the gene FNBP1 (BTA 11). Our results provide new information about the underlying biology and molecular mechanisms associated with HYP in Holstein cows.