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Abstract Background There is an increasing need to account for genotype-by-environment (G × E) interactions in livestock breeding programs to improve productivity and animal welfare across environmental and management conditions. This is even more relevant for pigs because selection occurs in high-health nucleus farms, while commercial pigs are raised in more challenging environments. In this study, we used single-step homoscedastic and heteroscedastic genomic reaction norm models (RNM) to evaluate G × E interactions in Large White pigs, including 8686 genotyped animals, for reproduction (total number of piglets born, TNB; total number of piglets born alive, NBA; total number of piglets weaned, NW), growth (weaning weight, WW; off-test weight, OW), and body composition (ultrasound muscle depth, MD; ultrasound backfat thickness, BF) traits. Genetic parameter estimation and single-step genome-wide association studies (ssGWAS) were performed for each trait. Results The average performance of contemporary groups (CG) was estimated and used as environmental gradient in the reaction norm analyses. We found that the need to consider heterogeneous residual variance in RNM models was trait dependent. Based on estimates of variance components of the RNM slope and of genetic correlations across environmental gradients, G × E interactions clearly existed for TNB and NBA, existed for WW but were of smaller magnitude, and were not detected for NW, OW, MD, and BF. Based on estimates of the genetic variance explained by the markers in sliding genomic windows in ssGWAS, several genomic regions were associated with the RNM slope for TNB, NBA, and WW, indicating specific biological mechanisms underlying environmental sensitivity, and dozens of novel candidate genes were identified. Our results also provided strong evidence that the X chromosome contributed to the intercept and slope of RNM for litter size traits in pigs. Conclusions We provide a comprehensive description of G × E interactions in Large White pigs for economically-relevant traits and identified important genomic regions and candidate genes associated with GxE interactions on several autosomes and the X chromosome. Implementation of these findings will contribute to more accurate genomic estimates of breeding values by considering G × E interactions, in order to genetically improve the environmental robustness of maternal-line pigs.