Integrative meta-GWAS and lipidomics reveal genetic regulators of nutritional fatty acids and lipid metabolites in chicken liver lipid accumulation

The genetic basis of lipid metabolism in the poultry liver, the main site of fat synthesis, is poorly understood. We combined a meta-analysis of genome-wide association studies (meta-GWAS) of 1,636 broilers with deep lipidomic profiling of 320 livers, identifying 18 quantitative trait loci (QTLs) for abdominal fat percentage (AFP) and thousands of metabolite-associated loci. Mendelian randomization prioritized causal lipids, with docosahexaenoic acid (DHA), phosphatidylserine (PS), and triglycerides showing the strongest effects. Fine-mapping and functional validation identified non-synonymous variations in FAM161A , CD38 , and MRPL44 as key regulators of DHA, PS, and glyceride levels, respectively. This multi-omics map provides novel molecular targets for breeding programs to reduce abdominal fat while enhancing valuable fatty acids like DHA, thereby improving the nutritional quality of chicken meat. • A high-resolution hepatic lipid atlas was established by the large-scale mGWAS in chicken. • Novel genes ( FAM161A , CD38 , MRPL44 ) regulating lipid metabolism were identified and validated, especially a key genetic variant in FAM161A was found to control the level of DHA (omega-3 fatty acid). • Provides molecular targets to improve meat quality at the primary site of lipid synthesis.