The observation that many GWAS loci overlapped with eQTL specific to induced cells (Fig. 5D) is consistent with the hypothesis that disease risk alleles may manifest activity in a context-specific manner (36, 37). Noteworthy examples we identified include a unique cis-eQTL to the serine threonine kinase gene ATM after exposure to IFNγ (rs609261, P = 7.8 × 10−89) in complete LD to a GWAS SNP for metformin response in diabetes (38). Notably, IFN-γ has been shown to activate the ATM pathway (39), and ATM itself plays a key role in the IFN-γ response (40). Our data suggest that differential expression of ATM may be driving this association with metformin response in a highly context-specific manner.
