A scalable framework for single-cell eQTL mapping uncovers genetic regulators of meat production traits in pigs

Background Genetic determinants that regulate molecular phenotypes and complex traits often act in a highly context-dependent manner, and the underlying cell-type-specific regulatory mechanisms remain incompletely understood. Results In this study, we analyzed 42 single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) datasets from pig skeletal muscle. Through systematic benchmarking, we optimized a robust workflow for SNP calling and genotype imputation tailored to sc/snRNA-seq data, achieving high accuracy and computational efficiency. We constructed a comprehensive single-cell atlas of skeletal muscle that delineates cellular components and developmental trajectories, and identified 5,020 significant single-cell expression quantitative trait loci (eQTLs). By integrating phenotypic data from the PigGTEx project and performing phenome-wide association studies (PheWAS), we further pinpointed three candidate loci significantly associated with meat quality and growth traits whose effects were dependent on cell type. Conclusions This work offers a scalable computational framework for single-cell eQTL mapping and characterizes cell-type-specific associations between genetic variation and gene expression relevant to economically important traits in livestock, thereby providing functional context in particular for non-coding variants implicated by GWAS and helping to inform genomic selection and precision genome editing.