HLA genes play a critical role in the processing and presentation of antigens, they are highly polymorphic and show robust association with disease but the functional basis of this remains unresolved. Here we describe several striking associations to the MHC region (p<1×10−11), segregating by HLA allele, which may provide insights into the basis of associations with ulcerative colitis, rheumatoid arthritis and T1D. We describe a trans-association of AOAH, encoding acyloxyacyl hydrolase lipase that degrades bacterially derived lipopolysaccharide35, to the MHC class II region. An association between the MHC and AOAH has recently been described in a study of whole blood RNA from a mixed population of disease and control cohorts (peak eSNP rs2395185, 7.0×10−38)14. We replicate this finding at this SNP (rs2395185 pmonocyte=5.7×10−39), with the most strongly associated eSNP in our dataset being rs28366298 (pmonocyte=1.6×10−43). Notably, we find only very weak association of this region in B-cells (pB-cell>1×10−3) (Figure 5a), suggesting much of the signal in whole blood studies is monocyte derived, and providing underlying potential mechanistic insight. To further define this trans-association we inferred the underlying HLA alleles to
