Monocytes have evolved to scavenge and present antigens through a highly conserved endosomal pathway. This is assisted via the release of hydrolyzing enzymes from secretory granules. Lysozyme forms a key component of monocyte secretory granules and degrades bacterial cell wall derived peptidoglycan. We find evidence of a novel master regulatory region involving cis- and trans-eQTL at the 12q15 locus for rs10784774 and associated eSNPs spanning LYZ, encoding lysozyme (Figure 3). This locus forms a monocyte specific cis-eQTL (Supplementary Figure 9) to a probe mapping to the 3′ UTR of LYZ (pmonocyte=8.9×10−78) and forms a trans eQTL to a remarkable 62 annotated genes (72 probes) throughout the genome at a p<1×10−11, the most significant association being to the gene CREB1 (pmonocyte=2.03×10−67) and many others at a lower significance (Figure 3, Supplementary Figure 10 and Supplementary Table 5). Interrogation of a previously published primary cell eQTL analyses of negatively selected monocytes from whole blood10 and whole blood RNA from a mixed disease and control cohort14 replicates this strong association between 12q15 and expression of both LYZ and CREB1 (CREB1, p=5.1×10−22 (rs11177644) monocytes10;
