Figure 2. eQTL in genes involved in neutrophil biology.

As a narrative resource, we compiled a list of 164 genes of importance in neutrophil biology ^29,30,41-43 and illustrate their role together with eQTL information (denoted be gene colour). Probes for 113 genes passed QC: 9 genes had no eQTL (black gene names) and 104 had an eQTL (47 with FDR<0.05 red gene names, 57 with p<0.05 but FDR>0.05 purple gene names). Genes involved in nearly every aspect of neutrophil biology have identifiable eQTL and several are involved in Mendelian disorders (asterisked genes) for example RAC2 (neutrophil immunodeficiency syndrome) and FAS (autoimmune lymphoproliferative syndrome type 1A). (a) Granulocyte-monocyte progenitor cells (GMP) respond to GM-CSF stimulation of a receptor encoded by CSFR3 to form neutrophils under the instruction of CEBPα and other CEBP transcription factors. Neutrophil development through various stages is coincidental with expression of proteins that traffic to primary secondary and tertiary granules. (b) AP heterotetramers are involved in trafficking of proteins such as LYZ (involved in renal amyloidosis) and MMP9 (involved in metaphyseal osteolysis, nodulosis and arthropathy) to (c) primary, secondary and tertiary granules. (d) Hyper-segmented neutrophils egress from the bone marrow in response to IL-8 and SDF-1, and are (e) captured on endothelium within blood vessels through interaction of selectins and ligands such as SEKPLG and SELL. (f) Capture, rolling and eventual arrest on endothelial surfaces is associated with activation, mediated in part by PI-3 and MAPK pathways. (g) Arrest of neutrophils is mediated by α1β2/αMβ2 integrin heterodimers encoded by ITGAL, ITGBA2, ITGAM and (h) rapid para- and trans-cellular migration ensues. (i) Neutrophils express pattern recognition receptors and receptors for host derived molecules allowing detection of bacteria and effective migration. In tissues, neutrophil response includes (j) cytokine secretion, (k) oxidative burst, (l) phagocytosis, (m) production of neutrophil extracellular traps (NETosis), (n) pyroptosis, (o) autophagy, (p) cross-talk with other immune, and eventual cell death via apoptosis should cell death not have eventuated from another response. Box lower and upper border denote 25^th and 75^th centiles respectively, central line denotes median and whiskers extend to 1.5*IQR. In all cases 101 donor replicates shown.