Common regulatory variation impacts gene expression in a cell type dependent manner

Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (SNPs) on three cell types of 85 individuals. After excluding 10 outlier individuals detected through principal component analysis, we detected cell type-specific genetic effects, with 69 - 80% of regulatory variants operating in a cell type-specific manner and identified multiple eQTLs per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type specific eQTLs were found at larger distances from genes and lower effect size similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell type specificity. Total RNA was extracted from fibroblasts, LCLs, and T-cells of the 85 unrelated individuals of the GenCord. Two one-quarter scale Message Amp II reactions (Ambion, Foster City, CA) were performed for each RNA extraction with 200 ng of total RNA. 1.5 μg of cRNA was hybridized to a commercial whole-genome expression array (WG-6 v3 Expression BeadChip, Illumina) to quantify transcript abundance. In total there were two technical replicates (labeling and hybridization) for each RNA sample.