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Identifying Genomic Regulators of Set-Wise Co-Expression

The genetical genomics approach has been used to study the genetic basis of variation in gene expression, where putative transcriptional regulators of genes are identified via genetic quantitative trait mapping. The genetic regulators identified through such efforts can partially account for an individual gene's natural variation. However, genes in a molecular pathway often exhibit coordinated activities, the patterns and levels of which are also regulated. In an effort to understand these complicated mechanisms, we propose a method that searches for the genomic regulators of set-wise co-expression of related genes, based on current genetical genomics data. Using this method, we studied genomic regulators of 233 biological pathways for a BXD RI data set. For 15 pathways, we obtained significant regulatory loci after controlling for the false discovery rate. The results presented in this paper constitute important evidence of the heritability of mRNA co-expression between individuals. We have shown that, by defining new phenotypes using existing genetical genomics data, evidence on regulation of co-expression can be derived.