All genes in table 1, excluding PTPRE and KCNN4 (discussed below), have been either previously reported with GWAS studies, or are located in the vicinity of reported genes (within 1MB). About 35% of all GENCODE protein-coding genes are reported (in the NHGRI catalog) or within 1 MB of a reported gene as associated with a WTCCC disease. For T1D, 5 out of the 29 genome-wide significant genes have been reported via conventional single variant analyses (as curated by the NHGRI25 repository of GWAS results). Furthermore, 21 of the genes associated with T1D in our analysis lie within the extended MHC (Table 1), a region that is known to be associated with disease risk26. Additionally, ERBB3, which contains SNPs previously associated with T1D in GWAS27, showed a negative correlation with disease risk in PrediXcan (p < 10−11), which is consistent with a prior study that showed risk genotypes associated with lower expression of ERBB3 in PBMCs28. Furthermore, it has been reported that subjects with protective genotypes had higher percentages of ERBB3+ monocytes and dendritic cells leading to greater T cell proliferation28. These results highlight one of the key advantages of PrediXcan, which is to provide the direction of effect.
