This study reveals trans-eQTLs possess an even higher degree of cellular autonomy than cis, reflecting them manifesting as products of upstream gene expression and cellular cross-talk. Notably, we identify novel master-regulatory regions specific to monocytes via LYZ and B-cells via the expression of KLF4. The functional implications with respect to infectious disease susceptibility of the multi-locus LYZ eQTL remain to be explored, but the existence of several genes including ERAP2, encoding an aminopeptidase involved in the loading of class I MHC molecules55 as well as RAB27A, encoding a GTPase critical to the membranous tethering of secretory lysosomes56, would suggest this eQTL may impact upon antigen presentation. The identification of B-cell specific trans-eQTLs to rs11717139, a locus with reproducible association to autoimmune diseases, in genes with putative roles in cell-cycle and apoptosis provides novel candidate genes for analysis in autoimmune disease susceptibility. B-cells are intrinsically prone to apoptosis providing protection against the generation of self-reactive antibodies. Regulation of genes involved in apoptosis would therefore be predicted to alter this process and predispose to autoimmunity57. It is notable that these genes do not have strong cis-eQTLs which otherwise might be expected to be disease associated.
