Integrating Epistatic Interactions into Genomic Prediction of Growth and Fillet Fat Content in Common Carp.

Common carp (Cyprinus carpio) is an important freshwater aquaculture species, yet non-additive genetic effects remain poorly understood for economically important traits. Here, we dissected epistatic interactions affecting standard body length (SL) and fillet fat content (FC) by integrating pathway-level epistasis analysis, genomic selection (GS), and AlphaFold2 (AF2)-based structure prediction. BridGE analysis detected extensive epistatic signals for both traits. Incorporating selected interactions into GS models improved predictive ability within the sampled population, yielding correlations of 0.85 for SL and 0.87 for FC. An epistasis-informed reduction strategy downsized the initial 2.2 million SNPs to 12,902 candidate markers while retaining useful predictive information. AF2-based predictions provided complementary structural support for a subset of candidate driver interactions. Network and enrichment analyses further revealed distinct molecular features associated with SL and FC. Together, these findings suggest that incorporating epistatic information can improve genomic predictive ability of complex traits in common carp, and provide a basis for further evaluation of epistasis-informed selection in independent aquaculture populations.