Heritability Patterns of Protein-Coding Genes Expression: Insights From the Pig Genotype-Tissue Expression Project

Understanding the genetic basis of gene expression is crucial for elucidating the mechanisms underlying complex traits, especially for protein-coding genes (PCGs) whose expression levels directly affect protein abundance and functionality. Recent studies have improved our understanding of local (cis-) and distal (trans-) regulatory mechanisms that control gene expression levels. However, a comprehensive understanding of the heritability patterns of PCG expression in pigs, which are valuable models for human biology, remains lacking. In this study, we used genomic and transcriptomic data from 4760 pigs across 13 tissues from the Pig Genotype-Tissue Expression (PigGTEx) project and applied linear mixed models (LMMs) to estimate cis-, trans-, and global- heritability of PCG expression. Our findings indicate the average cis-heritability of gene expression across all tissues is 0.13, whereas the trans- and global-heritability are significantly higher, at 0.64 and 0.67, respectively. While variants in cis-regulatory regions explain only a minor proportion of expression variance, a single variant with stronger effects is predominantly located near transcription start sites (TSS). In addition, the heritability of gene expression captures information about both expression levels and independent cis-expression quantitative trait loci (cis-eQTL). Comparing housekeeping genes (HKGs) and tissue-specific genes (TSGs), we found that HKGs are influenced by genetic variants across the genome, whereas TSGs are mainly affected by variants near their cis-regions in most tissues. This study is a comprehensive analysis of gene expression heritability across multiple pig tissues, enhancing our understanding of genetic regulation in pigs.