Maternal care style in the Thoroughbred horse is linked to genetic variation at the glucocorticoid receptor gene (NR3C1) locus

Maternal care in the early post-natal environment has long-lasting effects on the resulting behavioural phenotype in mammalian species. In horses, maternal care is centered around protection and nursing behaviours. As well as epigenetic effects and indirect effects from offspring on maternal care, there is a large heritable contribution in other species. To test the hypothesis that the maternal care style (MCS) of a mare is influenced by direct genetic factors, MCS (High vs. Low) was determined for Thoroughbred mares by characterising protective and nursing behaviours validated against behavioural tests assessing maternal bond and fearfulness. SNP-array derived genotype data for n = 19 High MCS (9.2 ± 3.2 years, n = 3 primiparous) and n = 12 Low MCS (10.8 ± 4.8 years, n = 2 primiparous) mares were used to perform a composite selection signals test (XP-EHH, F ST , and ΔSAF) to identify genomic regions of interest (ROIs) with variable allele frequency spectra between the two cohorts. Thirteen ROIs were identified containing candidate genes with biological functions in stress, anxiety, and depression. The top SNPs in 11 ROIs were significantly ( P < 0.05) associated with Low MCS. The largest genotypic effect (GG-genotype 66.7% Low MCS, 5.3% High MCS; odds ratio [OR] = 0.028, 95% CI 0.003–0.290, P = 0.021) was identified for a SNP on chr10 close to HMGN3 that influences anxiety-related behaviours in mice. A ROI on chr14 contained NR3C1 , encoding the glucocorticoid receptor, that has a central role in modulating the effect of the maternal care environment. The C-allele for the top SNP in the ROI (rs68988173) occurred at a frequency of 79.2% and 42% in Low MCS and High MCS, respectively. Among n = 933 horses from 34 horse breeds and Przewalski horse the rs68988173 C-allele was most common in the Thoroughbred (66%) and the CC genotype was absent in most landrace breeds and in Przewalski horse. Following validation of these genetic makers in independent, well-phenotyped cohorts, they may have value for identifying mares, particularly primiparous mares, with a potential genetic risk of Low MCS, to inform proactive management strategies in the early post-natal period.