Feb 2, 2012

Dissecting the regulatory architecture of gene expression QTLs

Genome Biology
Daniel J GaffneyJonathan K Pritchard

Abstract

Expression quantitative trait loci (eQTLs) are likely to play an important role in the genetics of complex traits; however, their functional basis remains poorly understood. Using the HapMap lymphoblastoid cell lines, we combine 1000 Genomes genotypes and an extensive catalogue of human functional elements to investigate the biological mechanisms that eQTLs perturb. We use a Bayesian hierarchical model to estimate the enrichment of eQTLs in a wide variety of regulatory annotations. We find that approximately 40% of eQTLs occur in open chromatin, and that they are particularly enriched in transcription factor binding sites, suggesting that many directly impact protein-DNA interactions. Analysis of core promoter regions shows that eQTLs also frequently disrupt some known core promoter motifs but, surprisingly, are not enriched in other well-known motifs such as the TATA box. We also show that information from regulatory annotations alone, when weighted by the hierarchical model, can provide a meaningful ranking of the SNPs that are most likely to drive gene expression variation. Our study demonstrates how regulatory annotation and the association signal derived from eQTL-mapping can be combined into a single framework. We used th...Continue Reading

  • References68
  • Citations117

Citations

Mentioned in this Paper

Quantitative Trait Loci
HapMap
Genome
Promoter
Gene Expression
Chromatin Location
Dornavac
Bayesian Prediction
DNA Helix Destabilizing Proteins
Promoter Regions, Genetic

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.