These trans-eQTLs provide valuable insight on previously unknown functional downstream consequences trait-associated SNPs have, e.g. rs2395185 is the strongest susceptibility variant for ulcerative colitis [27] (UC) but also the strongest SNP, trans-acting on Acyloxyacyl hydrolase (AOAH, p = 1.0×10−36), an enzyme that modulates host inflammatory responses to gram-negative bacterial invasion. It is known that deficiencies in response mechanisms against bacterial products like lipopolysaccharide, present on gram-negative bacterial cell walls, play an important role in UC disease pathogenesis [28]. Within the peripheral blood we observed that AOAH is significantly co-expressed with colony stimulating factor 1 receptor (CSF1R, r = 0.21) and major histocompatibility complex class II DR alpha (HLA-DRA, r = 0.19). Hyperstimulation of CSF1R has been implicated in UC [29], while HLA-DRA is one of the positional UC candidate genes mapping in very close proximity to rs2395185. Another UC HLA variant, rs9268877, was trans-acting on T cell receptor beta variable 18 (TRBV18), part of the TCRß locus at 7q34. It is known that TCRß mutant mice develop chronic colitis [30].
