Multi-trait GWAS of reaction norm parameters reveals environment-responsive loci influencing reproductive performance in heifers

Reproductive efficiency in Nellore heifers is fundamental to the profitability and sustainability of beef production in tropical regions, where environmental stress can cause genotype-environment (G×E) interactions that affect fertility. Using 200,258 and 299,885 phenotypic records for heifer early pregnancy (HP) and heifer rebreeding (HR), respectively, we investigated the genetic basis of reproductive plasticity via single-step genomic reaction norms across a continuous environmental gradient (EG) defined from yearling weight records as a proxy for environmental quality. Genomic analyses included 22,556 animals (21,456 females and 1,100 sires) with genotypes imputed to 409,617 single-nucleotide polymorphisms (SNPs). We then performed genome-wide association analyses of the reaction norm intercept (genetic merit) and slope (environmental sensitivity), followed by multi-trait summary analyses and Bayesian fine-mapping of significant loci using imputed whole-genome sequence variants within ±100 kb windows around lead SNPs.

Heritability for both traits increased with environmental quality, indicating environment-dependent expression of genetic variance. Genetic correlations for HP and HR across the environmental gradient ranged from 0.15 to 0.98, supporting substantial G×E interactions and reranking between low and high environmental conditions. Multi-trait analyses of reaction norm parameters identified 482 significant signals for the intercept and 700 for the slope. Intercept-associated loci were enriched for lipid metabolism, embryonic development, estrous regulation, and hypothalamic–pituitary signaling, whereas slope-associated loci highlighted endocrine signaling, metabolic plasticity, and neuroendocrine feedback responsive to contrasting post-weaning nutritional and management conditions captured by the EG. Fine-mapping refined associations to 146 (intercept) and 149 (slope) putative loci for HP, and 117 (intercept) and 167 (slope) for HR, supported by high posterior probabilities and Bayes factors. Candidate variants mapped to endocrine and metabolic regulators, including IGF1, LEP, GHRL, GNRHR, KISS1, MAPK3, PLAG1, INSR, and LHCGR.

G × E interactions play a key role in shaping the genetic architecture of reproductive efficiency in Nellore heifers. Integrating reaction norm, multi-trait GWAS, and fine-mapping highlighted loci, affecting both genetic merit and environmental sensitivity of fertility, providing targets to select more resilient Nellore females for tropical systems.