A sequence-based genome-wide association study for dominance effects on fertility traits in Holstein cattle

Fertility traits are crucial economic traits in dairy cattle production, with a substantial influence on farm profitability. As quantitative traits, fertility traits are affected by both genetic and environmental factors. While previous studies have primarily focused on additive genetic effects, the contribution of dominance effects on key economic traits in Holstein cattle remains insufficiently explored. This study employed a genome-wide association study to simultaneously evaluate additive and dominance effects. The objectives were to identify Single-Nucleotide Polymorphism (SNP) loci and genes associated with fertility traits, detect genetic markers affecting fertility traits in Chinese southern Holstein cattle, and enhance the understanding of their underlying genetic mechanisms. Using high-quality imputed whole-genome sequence data from 3 439 individuals, we analysed eight fertility traits. Genome-wide association analyses identified 720 SNPs exhibiting significant additive effects and 505 with significant dominance effects, among which 465 SNPs overlapped. Notably, dominance effects independently captured 13 candidate genes (including 3 regulated exclusively by dominance) and uncovered non-additive variation that additive-only analyses missed. Functional annotation highlighted 21 candidate genes, such as LY6E, LY6K, GPR12, PSME4, CYP11B1, CHAC1, and GUSB. Among these, ten genes were regulated by both effects, eight by additive effects alone, and three by dominance effects alone. Gene ontology and kyoto encyclopedia of genes and genomes analyses showed these genes are involved in reproductive biological processes-such as steroid hormone synthesis, fertilisation, gastrulation, primary germ layer development and are enriched in pathways related to reproductive endocrine regulation, fatty acid metabolism, neural signal transduction, and oxidative stress. Fine-mapping and Linkage Disequilibrium (LD) analysis further refined key genomic regions, including a locus on chromosome 11 at position 36.3-36.9 Mb associated with conception rate, and identified core candidate SNPs such as chr14:1525338 near LY6E. This study demonstrates that incorporating dominance effects enhances the detection power of genetic associations and provides a more complete characterisation of the genetic architecture of fertility traits. Our findings offer a robust foundation for genomic prediction, advancing the accuracy of breeding programmes targeting fertility improvement in Holstein cattle.