Integration of GWAS and eQTL analysis reveals regulatory CNVs for fatty acid traits in cattle

Fatty acid (FA) composition is critical for meat quality and flavor. The regulatory role of copy number variations (CNVs) in bovine FA traits remains underexplored. Here, we integrated CNV-based genome-wide association studies (GWASs) with expression quantitative trait locus (eQTL) analysis to clarify the function of CNVs in bovine FA metabolic regulation. Using Bovine HD SNP array and RNA-seq data, we identified 21 CNVs significantly associated with 21 FA traits. Notably, a 278.6-kb duplicated CNV region (CNVR) on BTA13 was linked to the increase in docosanoic acid (C22:0) levels, and this region harbors ECHDC3, a gene highly expressed in the muscle, liver, and adipose tissues. Integration of SNP-GWAS and tissue-specific CNV-based eQTL data further confirmed ECHDC3 and AGPAT3 as key regulators of FA metabolism. Finally, cellular knockdown experiments further validated their synergistic interaction and suggested a compensatory regulatory mechanism. Our findings provide insights into CNV-mediated genetic regulation of meat quality traits in livestock.