PSIV-B-21 - Genome-wide Association Studies for Ketosis in Dairy Cattle

Abstract: Lactating dairy cows often experience a negative energy balance (NEB) and must mobilize adipose reserves to adapt to this metabolic stress. Dairy cows that are unable to adapt to this NEB often suffer from metabolic disorders such as ketosis causing significant financial losses due to a reduction in milk production, poor reproductive performance, and an increased risk of developing other disorders. Therefore, the aim of this study was to identify genes and their associated biological pathways to better understand the molecular genetic basis for the development of ketosis. Genome wide association studies analysis was performed using a mixed linear model on 436 Jersey and Holstein cows ranging in ketosis history and genotyped for high density single nucleotide polymorphisms (SNPs) panel. After quality control, 409 with 617,527 SNPs were included in further analyses. The association analysis was performed using a mixed linear model implemented in GCTA software and fitting SNP, breed, and pen as fixed effects with animal as random effect. The top 100 significant SNPs (P < 0.0003) were mapped to 29 genes. Gene enrichment analyses were conducted using DAVID software to determine biological pathways enriched for the identified list of genes. The genomic heritability estimated in this study was 0.17 indicating existence of genetic influence on ketosis in animals in this herd. The analyses revealed candidate genes to be involved in biological pathways involving coronary vascular development, platelet activation and aggregation and osteoclast differentiation. The results indicated a relationship between ketosis development and the immune system or development of other diseases. Further research is needed to validate the identified biological mechanisms underlying the variation between cows for ketosis incidence and progression in dairy cows.