Genome-wide association analysis of heifer livability and early first calving in Holstein cattle

Authors: GAO, YAHUI - University Of Maryland; MARCEAU, ALEXIS - University Of Maryland; IQBAL, VICTORIA - University Of Maryland; TORRES-VAZQUEZ, JOSE - University Of Maryland; Neupane, Mahesh; JIANG, JICAI - North Carolina State University; Liu, Ge - George; MA, LI - University Of Maryland

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/2023
Publication Date: 10/21/2023
Citation: Gao, Y., Marceau, A., Iqbal, V., Torres-Vazquez, J.A., Neupane, M., Jiang, J., Liu, G., Ma, L. 2023. Genome-wide association analysis of heifer livability and early first calving in Holstein cattle. BMC Genomics. 24:628. https://doi.org/10.1186/s12864-023-09736-0.
DOI: https://doi.org/10.1186/s12864-023-09736-0

Interpretive Summary: We do not understand cattle health and reproduction traits well. In this study, we performed a genome-wide association study and found a major quantitative trait lcous for a reproduction trait. These results fill our knowledge gaps and provide the foundation for incorporating new markers into the future animal breeding program. Farmers, scientists, and policy planners who need to improve animal health and production based on genome-enabled animal selection will benefit from this study.

Technical Abstract: Background: The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, the Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has not been fully studied. Results: Leveraging the large U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27K bull with imputed sequence variants. Since there are few major QTL for these traits, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. Conclusion: Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.