Where Are the Disease-Associated eQTLs?

Most disease-associated variants, although located in putatively regulatory regions, do not have detectable effects on gene expression. One explanation could be that we have not examined gene expression in the cell types or conditions that are most relevant for disease. Even large-scale efforts to study gene expression across tissues are limited to human samples obtained opportunistically or postmortem, mostly from adults. In this review we evaluate recent findings and suggest an alternative strategy, drawing on the dynamic and highly context specific nature of gene regulation. We discuss new technologies that can extend the standard regulatory mapping framework to more diverse, disease-relevant cell types and states.

Automated summary

Most disease-associated genetic variants, even though located in potentially regulatory regions, do not show detectable effects on gene expression. This could be due to the fact that gene expression has not been examined in the most relevant cell types or conditions for the disease. Current large-scale efforts to study gene expression are limited to human samples obtained opportunistically or postmortem, usually from adults.