We also identified 47 GWAS traits for which at least four independent variants affected the same gene in trans (Supplementary Table 8–10), 3.4-times higher than expected by chance (P=0.001; two-tailed two-sample test of equal proportions). For systemic lupus erythematosus (SLE)30, the expression of IFIT1, IFI44L, HERC5, IFI6, IFI44, RSAD2, MX1, ISG15, ANKRD55, OAS3, OAS2, OASL and EPSTI1 was affected by at least three SLE-associated genetic variants (FDR<0.05). These genes are nearly all known interferon genes in the SLE interferon signature31–33 (Supplementary Table 11), reflecting the involvement of interferon signaling in SLE pathophysiology (Figure 5). While the trans-eQTL analysis identified only one novel interferon signature gene, it helped to pinpoint SLE GWAS loci that collectively affect interferon signature genes.
