Integrative analysis of GWAS and transcriptome reveals p53 signaling pathway mediates resistance to visceral white-nodules disease in large yellow croaker

Visceral white-nodules disease (VWND), caused by Pseudomonas plecoglossicida, is one of the primary causes of morbidity and mortality in large yellow croaker aquaculture. Host disease resistance is a heritable trait that involves complex regulatory processes. However, the regulatory mechanism of bacterial resistance in large yellow croaker is still unclear. This study attempted to systematically evaluate the major genetic loci and transcriptional regulatory mechanisms associated with the resistance to VWND in large yellow croaker by crossover method studies. A large population of large yellow croaker was challenged with P. plecoglossicida, with survival time recorded and samples were taken for genotyping. Meanwhile, spleen samples that were used for RNA-seq to compare their transcriptomic profiles before and after infection were taken from resistant populations (RS) and susceptible control populations (CS) bred using the genomic selection (GS) technique. Genome-wide association analyses using 46 K imputed SNP genotypes highlighted that resistance is a polygenic trait. The integrative analysis results show the co-localization of the cd82a gene between disease resistance-related genetic loci and comparative transcriptional analysis. And functional enrichment analysis showed differential enrichment of the p53 signaling pathway in RS and CS groups, suggesting that there may be cd82a-mediated p53 signaling pathway activation for VWND resistance. This large-scale study provides further evidence for the heritability and transcriptional regulatory mechanisms of host inheritance of VWND resistance.