Genetic parameters and QTL mapping for novel metabolic traits in early-lactation Holsteins

Early lactation in dairy cows is characterized by negative energy balance and compromised immune function that could lead to metabolic or inflammatory diseases. Circulating biochemical blood variables are increasingly used as indicators of metabolic and inflammatory diseases in many species. This study aimed to estimate genetic parameters and identify candidate genes and quantitative trait loci (QTL) associated with serum proteins (total protein, albumin, globulin, and albumin-to-globulin ratio), liver enzymes (gamma-glutamyltransferase [GGT], aspartate-amino-transferase [AST], glutamate dehydrogenase [GLDH]) and other serum variables (glucose, urea, nonesterified fatty acids [NEFA], β-hydroxybutyric acid [BHBA], and cholesterol). The study population consisted of genotyped lactating Holsteins (938 cows with 80,709 single nucleotide polymorphisms [SNPs]) and serum concentrations of biochemical variables sampled at 2-14 days in milk (DIM) from 11 commercial farms in Alberta. The heritability of the serum variables ranged from 0.04 to 0.35, with cholesterol the most heritable (0.35 ± 0.07), while both glucose and urea were the least heritable (0.04 ± 0.05). Strong genetic correlations were observed between NEFA and GGT (0.78 ± 0.34), AST (0.74 ± 0.29), and BHBA (0.70 ± 0.26). Genome-wide association studies (GWAS) identified 45 and 7 SNPs associated with GGT and cholesterol concentrations, respectively. Candidate genes and QTLs within 100 kb up- and downstream of significant SNPs were detected for GGT and cholesterol. Multiple candidate genes and QTLs in the identified regions are implicated in pathways influencing metabolic disorders, production, and fertility in lactating dairy cows. Overall, the results showed low-to-moderate heritability and identified candidate genes and QTL regions associated with serum GGT and cholesterol. These results have potential utility in efforts to enhance the resilience of dairy cows through genetic selection.