Gene function & annotation

Case-control GWAS identifies variants affecting stillbirths in Icelandic Dairy Cattle

---

Abstract

Frequency of stillbirths in Icelandic Dairy Cattle has increased over the past decades. It is possible that the increase is partly caused by lethal recessive mutations. Recently, regions of homozygote haplotype deficiency (HHD) were detected in the population. By combining a genome-wide association study (GWAS) of stillbirth, HHD analysis, and analysis of runs of homozygosity (ROH), it is possible to identify genetic variants associated with stillbirth. The objective of this study was to identify genomic regions affecting stillbirths and select stillborn calves for whole-genome sequencing to identify causal mutations. To achieve these objectives, we conducted a case-control GWAS and analysed ROH. Tissue samples from 92 stillborn calves were collected from 26 Icelandic dairy farms and genotyped with the EuroGenomics MDv6 SNP chip. We removed markers and individuals with less than 95% call rates, individuals with extreme heterozygosity, and removed markers with minor allele frequency less than 1%. We combined the genotypes of stillborn calves (cases) with genotypes of liveborn animals (controls). The samples were filtered so that no pair of liveborn animals had proportion of identity-by-descent over 0.06 and no pair of stillborn animals over 0.25. This filtering resulted in 61 cases and 696 controls genotyped at 37,549 markers on 29 autosomes that were used for a single-marker based association study. We also conducted a gene-based associated study, testing the association of 10,204 genes with stillbirth using a likelihood ratio test. To study ROH coverage, we did not filter for minor allele frequency or relationships. We evaluated ROH using a window-based method implemented in the R-package detectRUNs using 78 stillborn calves and 30,817 liveborn calves. Only ROH longer than 2Mb and 20 SNPs or more were considered. Sixty-four markers on 24 autosomes were significant in the GWAS and 42 genes on 19 autosomes according to the gene-based analysis. The most prominent significant peaks were on BTA8 around 96.8 Mb and BTA19 around 56.8 Mb, and non-significant, suggestive peaks at BTA3 around 114.5 Mb and BTA13 around 43.7 Mb. Significant markers overlapped with regions of homozygous haplotype deficiency on BTA3, BTA7, BTA8, BTA13 and BTA19. We found 10 regions on 8 autosomes that are promising for further study. We identified positional candidate genes that have been associated with fertility and conformation, including GRB2, ATRN, ST8SIA4 and SH3BP4. Genotypic frequencies of associated markers did not suggest the presence of recessive lethal alleles. We did not find clear evidence of ROH-based inbreeding on stillbirth. Our findings indicate that stillbirth in Icelandic Cattle is a highly polygenic trait. Some of the candidate genes have been associated with pregnancy-related disorders in other species.

Keywords: 2026

How to Cite:

Gautason, E., Jóhannesson, G. & Sahana, G., (2026) “Case-control GWAS identifies variants affecting stillbirths in Icelandic Dairy Cattle”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2285456. doi: https://doi.org/10.31274/wcgalp.23715

Rights: 1