Integrative lipidomic and genomic analysis identifies key lipids for wooden breast in chickens

Background Wooden breast (WB) is a prevalent myopathy in broilers that substantially reduces meat quality and causes considerable economic losses. However, the genetic architecture and lipidomic alterations associated with WB remain poorly understood. This study aimed to integrate untargeted lipidomics and genomic analyses to characterize lipid alterations and their associated genetic factors in WB. Results To characterize WB-related phenotypes, pectoralis major muscles from 312 broilers were evaluated for WB severity, compression force (CF), endomysium thickness, and total lipid abundance. By integrating differential abundance analysis, trend analysis, and weighted gene co-expression network analysis (WGCNA), we identified a core set of 25 lipid species. Further refinement using Mendelian randomization (MR) and mediation analyses prioritized nine lipids as candidate molecular traits associated with genetic variation and WB, seven of which showed consistent associations in an independent cohort ( n = 119). Metabolome genome‐wide association study (mGWAS) of these lipids identified a consensus genetic locus on chromosome 6 (19.55–20.15 Mb) shared by three candidate lipids. Integration of transcriptomic profiles from genes within this locus prioritized five candidate genes, with MAPK8 and NPY4R showing consistent expression patterns in the independent cohort. Based on its potential biological relevance, MAPK8 was selected for functional characterization in chicken primary myoblasts. MAPK8 overexpression and knockdown produced opposite effects on lipid accumulation, oxidative stress, and fibrosis-related gene expression, suggesting that MAPK8 may participate in cellular processes involved in lipid accumulation, oxidative stress, and fibrotic remodeling associated with WB. Conclusions This study provides an integrated overview of lipid metabolic alterations and their genetic architecture in WB-affected chickens. Collectively, these findings identify candidate lipid biomarkers and genetic loci and implicate MAPK8 as a candidate gene associated with lipid deposition and fibrotic remodeling in WB.