The MHC has been previously associated with trans-eQTL in primary tissues (8, 19). Trans associations to the MHC predominantly map to SNPs in the class II region and demonstrate plasticity across stimuli (Fig. 2 and fig. S9), with 45 genes mapping in trans (FDR < 0.05) to the class II region after IFN-γ treatment in the paired 228 data set, whereas after 24 hours of exposure to LPS, only one observation is made. Moreover, after IFN-γ treatment, we see the same trans-associating genes as in the naïve state, but almost all show increased effect sizes. The number of trans-associated genes mirrors class II expression, where IFN-γ and chronic LPS are associated with robust increases and suppression of class II gene expression, respectively (23) (fig. S9), suggesting that relative expression of class II genes may control trans effects.
