Functional Architectures of Local and Distal Regulation of Gene Expression in Multiple Human Tissues.
Genetic variants that modulate gene expression levels play an important role in the etiology of human diseases and complex traits. Although large-scale eQTL mapping studies routinely identify many local eQTLs, the molecular mechanisms by which genetic variants regulate expression remain unclear, particularly for distal eQTLs, which these studies are not well powered to detect. Here, we leveraged all variants (not just those that pass stringent significance thresholds) to analyze the functional architecture of local and distal regulation of gene expression in 15 human tissues by employing an extension of stratified LD-score regression that produces robust results in simulations. The top enriched functional categories in local regulation of peripheral-blood gene expression included coding regions (11.41×), conserved regions (4.67×), and four histone marks (p
|Year of Publication||
Am J Hum Genet
2017 Apr 06
|PubMed Central ID||
R01 MH107649 / MH / NIMH NIH HHS / United States
U01 MH109528 / MH / NIMH NIH HHS / United States