Over 60 loci have been reported as associated with Type 1 Diabetes (T1D). Many of these are defined only by anonymous SNPs: identity of the causative genes, and the molecular bases by which they mediate susceptibility, are not known. We performed a systematic analysis to characterize these genes. First, all known genes in modest linkage disequilibrium with the tagging SNP for each locus were tested for commonly occurring non-synonymous variations. We identified common non-synonymous alleles in 112 genes at 37 non-HLA T1D regions. Next, we examined the effect of SNP genotypes on regulating expression levels of nearby (<2Mb) genes (i.e. cis-regulatory effects typical of promoter/enhancer elements). To do so, we examined gene expression in a total of 442 samples of three different cell types: EBV-transformed B cell lines (resting and after PMA stimulation); and purified CD4+ and CD8+ T cells. We mapped cis-acting expression quantitative trait loci (eQTL) and found 35 non-HLA T1D-associated cis-eQTLs that affected the expression of 84 transcripts, typically with P < 5×10−4. Finally, we tested T1D- associated SNPs for trans-regulatory effects (i.e. association with changes in expression of genes located in other chromosomal regions). We found 51 non-HLA T1D-associated trans-eQTLs that significantly affected the expression of 1,162 transcripts with P < 1×10−9. In summary, our systems genetics analyses provide novel insights into the complex genetics of T1D, as well as defining candidate genes for further investigation.