RT Journal Article
SR Electronic
T1 Functional partitioning of local and distal gene expression regulation in multiple human tissues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 046383
DO 10.1101/046383
A1 Xuanyao Liu
A1 Hilary K. Finucane
A1 Alexander Gusev
A1 Gaurav Bhatia
A1 Steven Gazal
A1 Luke O’Connor
A1 Brendan Bulik-Sullivan
A1 Fred A. Wright
A1 Patrick F. Sullivan
A1 Benjamin M. Neale
A1 Alkes L. Price
YR 2016
UL http://biorxiv.org/content/early/2016/03/31/046383.abstract
AB Studies of the genetics of gene expression have served as a key tool for linking genetic variants to phenotypes. Large-scale eQTL mapping studies have identified a large number of local eQTLs, but the molecular mechanism of how genetic variants regulate expression is still unclear, particularly for distal eQTLs, which these studies are not well-powered to detect. In this study, we use a heritability partitioning approach to dissect the functional components of gene regulation. We make use of an existing method, stratified LD score regression, that leverages all variants (not just those that pass stringent significance thresholds) to partition heritability across functional categories, and we extend this method to partition local and distal gene expression heritability in 15 human tissues. The top enriched functional categories in local regulation of peripheral blood gene expression included super enhancers (5.18x), coding regions (3.73x), conserved regions (2.33x) and four histone marks (p<3x10-7 for all enrichments); local enrichments were similar across the 15 tissues. We also observed substantial enrichments for distal regulation of peripheral blood gene expression: super enhancers (1.91x), coding regions (4.47x), conserved regions (4.51x) and two histone marks (p<3x10-7 for all enrichments). Analyses of the genetic correlation of gene expression across tissues showed that local gene expression regulation is largely shared across tissues, but distal gene expression regulation is highly tissue-specific. Our results elucidate the functional components of the genetic architecture of local and distal gene expression regulation.