Genome-wide association and genomic prediction of antibody response to Edwardsiella piscicida vaccination in olive flounder (Paralichthys olivaceus)

Genetic improvement of disease resistance presents a transformative opportunity for sustainable aquaculture intensification, yet the genomic architecture of antibody responses and optimal genomic prediction strategies remain poorly characterized in commercially important finfish species. Here, we preliminarily investigated the genomic basis of post-vaccination Edwardsiella piscicida antibody levels in 566 olive flounder (Paralichthys olivaceus) genotyped with 55,758 single-nucleotide polymorphisms (SNPs). SNP-based heritability was low (h2 = 0.04-0.06), substantially lower than that of morphometric traits (h2 = 0.27-0.39), suggesting a complex genetic basis. Genome-wide association analysis identified chromosome-wide significant association signals on chromosome 10 (p -5), and haplotype analyses suggested two distinct linkage disequilibrium blocks. Functional enrichment of 34 candidate genes identified 20 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways (adjusted p< 0.05), including Notch signaling and cell adhesion molecule interactions. Among the nine genomic prediction models evaluated, Bayesian models achieved the highest cross-validated predictive ability. Comparison of marker pre-selection strategies across 10 marker densities (50-50,000 SNPs) indicated that genome-wide association study (GWAS)-based pre-selection using the full dataset inflated apparent accuracy through information leakage. In contrast, nested GWAS and random selection converged toward the all-marker baseline (r ≈ 0.25) at higher marker densities, with no pre-selection strategy showing a clear advantage at the current sample size. Family-stratified and leave-one-family-out cross-validation produced consistent across-family predictive ability estimates (r ≈ 0.25), underlining the importance of family-aware validation designs for realistic accuracy assessment in structured aquaculture populations. Together, these findings offer a preliminary basis for genomic selection of antibody-mediated immune traits in olive flounder, underscoring the importance of leakage-free, family-aware validation for accurate prediction assessment in aquaculture populations.