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 2 and 4 digit resolution in all individuals through genotype imputation36,37. This enables us to refine the association of AOAH expression and the MHC to the presence or absence of HLA class II alleles DRB1*04, *07 and *09 (p<2.2×10−16, 2 way ANOVA) which define HLA-DRB4 (Figure 5b, Supplementary Figure 13). Specifically, individuals homozygous for any of these alleles express 0.6 fold (95% C.I. 0.57-0.67) the level of AOAH as individuals homozygous for all other alleles at DRB1. Interestingly we observe a second monocyte-specific trans-association for DRB1*04/*07/*09 to ARHGAP24 (peak eSNP rs28366298 pmonocyte=4.59×10−14). ARHGAP24 encodes a negative regulator of Rho-GTPase activating protein implicated in cell migration38. Converse to AOAH, we observe that individuals homozygous for DRB1*04/*07/*09 alleles express 1.4 fold (95% C.I. 1.30-1.54) the level of ARHGAP24 than all other alleles. These alleles are associated with autoimmune disease susceptibility, as is HLA-DRB4 (defining the DR53 antigen)39,40. Our study shows that specifically monocytes from individuals with HLA-DRB4 have significantly reduced AOAH expression,
