Disease-associated loci share properties with response eQTLs under common environmental exposures.

Response eQTLs identified in differentiating human iPSC cultures exposed to environmental substances share properties with disease-associated loci, highlighting context-dependent regulation.

• Why it matters: Understanding how genetic variants influence disease risk requires insights into gene regulation under various environmental conditions, which are underrepresented in steady-state tissues.
• What they did: The study profiled 1.4 million cells from 51 human iPSC lines exposed to nicotine, caffeine, or ethanol, identifying hundreds of response eQTLs and their dynamic regulatory effects across cell types and differentiation stages.
• The result: Response eQTLs are enriched in distal enhancers, regulate genes under strong selective constraint, and coincide with disease-associated loci, suggesting that studying gene-environment interactions enhances interpretation of genetic risk factors.