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

IF 6.2 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agriculture and Food Research Pub Date : 2026-05-01 Epub Date: 2026-01-29 DOI:10.1016/j.jafr.2026.102673

Bingxing An , Na Luo , Peihao Liu , Limin Wei , Lingzhao Fang , Jie Wen , Guiping Zhao

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Abstract

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 1636 broilers with deep lipidomic profiling of 320 livers, identifying 18 genomic regions associated with 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 carcass quality of chicken meat.

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综合meta-GWAS和脂质组学揭示了鸡肝脏脂质积累中营养脂肪酸和脂质代谢产物的遗传调控因子

家禽肝脏是脂肪合成的主要部位，其脂质代谢的遗传基础尚不清楚。我们将1636只肉鸡的全基因组关联研究（meta-GWAS）与320只肝脏的深度脂质组学分析相结合，确定了18个与腹脂率（AFP）相关的基因组区域和数千个代谢物相关位点。孟德尔随机化优先考虑因果脂类，二十二碳六烯酸（DHA）、磷脂酰丝氨酸（PS）和甘油三酯显示出最强的影响。精细定位和功能验证鉴定出FAM161A、CD38和MRPL44的非同义变异分别是DHA、PS和甘油酯水平的关键调节因子。这种多组学图谱为育种计划提供了新的分子靶标，以减少腹部脂肪，同时增加DHA等有价值的脂肪酸，从而提高鸡肉的胴体质量。

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