GWAS-expression associations detected in one tissue can identify regulatory variants that may be active in other tissues that are directly engaged in the etiology of disease23,25,26. One example is the cis-linkages in peripheral blood with the T1D susceptibility locus at chromosome 12q13. The strongest expression association is with transcription of the RPS26 ribosomal protein gene, and network analyses have been employed to argue that this is the more likely diabetes candidate gene than the initially reported ERBB328. However, the strongest T1D association involves a different SNP than that associated with expression and/or splicing24 of RPS26. We further find that the same linkage group of eSNPs, centered on the rs10876864 in the SUOX gene 35kb from RPS26, is also associated in trans with half a dozen other RP26 paralogs (probably due to cross-hybridization), and with CCDC4 on chromosome 4, albeit at the suggestive significance level ofP = 3.5×10−10. Intriguingly, expression of RPS26 is only weakly correlated with that of the module of ribosomal proteins that differentiate locations (Supplementary Fig. 4b online), so this association does not contribute to the environmental effect on transcription of ribosomal protein genes.
