Identification of genomic regions and genes associated with subclinical ketosis in periparturient dairy cows

Jihwan Lee1, KwangHyeon Cho2, Kent Weigel3, Heather White3, ChangHee Do4, Inchul Choi4,*
Author Information & Copyright
1Dairy Science Division, National Institute of Animal Science, RDA, Cheon-an 31000, Korea.
2Department of Beef and Dairy Science, Korea National College of Agriculture and Fisheries, Jeonju-si 54874, Korea.
3Department of Animal and Dairy Sciences, University of Wisconsin, Madison, Wisconsin 53706, United States.
4Department of Animal and Dairy Sciences, Chungnam National University, Daejeon 34134, Korea.
*Corresponding Author: Inchul Choi, Department of Animal and Dairy Sciences, Chungnam National University, Daejeon 34134, Korea, Republic of. E-mail:

© Copyright 2023 Korean Society of Animal Science and Technology. This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Subclinical ketosis (SCK) is a prevalent metabolic disorder that occurs during the transition to lactation period. It is defined as a high blood concentration of ketone bodies (beta-hydroxybutyric acid ≥ 1.2 mmol/L) within the first few weeks of lactation, and often presents without clinical signs. SCK is mainly caused by negative energy balance (NEB). The objective of this study is to identify single nucleotide polymorphisms (SNPs) associated with SCK using genome-wide association studies (GWAS), and to predict the biological functions of proximal genes using gene-set enrichment analysis (GSEA). Blood samples were collected from 112 Holstein cows between 5 and 18 days postpartum to determine the incidence of SCK. Genomic DNA extracted from both SCK and healthy cows was examined using the Illumina Bovine SNP50K BeadChip for genotyping. GWAS revealed 194 putative SNPs and 163 genes associated with those SNPs. Additionally, GSEA showed that the genes retrieved by DAVID (Database for Annotation, Visualization, and Integrated Discovery) belonged to calcium signaling, starch and sucrose, immune network, and metabolic pathways. Furthermore, the proximal genes were found to be related to germ cell and early embryo development. In summary, this study proposes several feasible SNPs and genes associated with SCK through GWAS and GSEA. These candidates can be utilized in selective breeding programs to reduce the genetic risk for SCK and subfertility in high-performance dairy cows.

Keywords: Subclinical ketosis; GWAS; SNP; gene-set enrichment analysis; biomarker