Genetical genomics has been established to study genetic variation of gene expression. It treats transcript expression as a quantitative trait and identifies putative regulatory loci for the expression of each gene. It is, however, well known that biological functions are often carried out through concerted activity of multiple genes. Therefore, we studied genetic regulators of biological pathways in lymphoblastoid cells. To identify the association of genomic loci and pathways, we applied two genetical genomics approaches, principal component analysis (PCA) and the differential allelic co – expression (DACE) test. We found that PCA is inadequate to identify regulatory loci for functional pathways. Association between a principal component, which summarizes the expression of a certain pathway, and a given marker was observed only when a direct association existed between the marker and the gene contributing most to that principal component. Another approach was the DACE test, a meth...