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Chunk #23 — RESULTS — Disease associated HLA alleles underlie trans-associations to the MHC

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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.
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Finally, although HLA allele carriage is associated with haplotype specific expression patterns across the MHC42, the high density of SNPs across this region, especially within classical HLA genes, results in exclusion of many probes. For HLA-C, an eQTL has been reported for a SNP rs926494243 located 35kb upstream of the gene associated with HIV-1 viral load and AIDS progression43,44. Our array data suggests a significant cis-eQTL, common to both cell types, but is potentially confounded by SNPs in the probe sequence. To overcome this we performed quantitative RT-PCR across the cohort using primers to regions with minimal SNP density and discrete from the probe binding site. This demonstrated a significant eQTL for rs9264942 (p=7.4×10−9) in PBMCs consistent with previous findings43 but the most significant association for HLA-C mapped to rs10484554 (p=5.2×10−16) (Supplementary Figure 14a), a GWAS SNP showing highly significant association with AIDS progression45 and psoriasis46,47. HLA imputation analysis shows the cis-eQTL can be defined in terms of presence of HLA alleles C*0602 and C*1203 (Supplementary Figure 14b,c). Further investigation is required to resolve the role of HLA-C and genetic