title: Dissecting the regulatory architecture of gene expression QTLs.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our study demonstrates how regulatory annotation and the association signal derived from eQTL-mapping can be combined into a single framework. We used this approach to further our understanding of the biology that drives human gene expression variation, and of the putatively causal SNPs that underlie it.
authors.affiliation: Department of Human Genetics, University of Chicago, 920 E58th Street, Chicago, IL 60637, USA. dg13@sanger.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gaffney
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Veyrieras
authors.forename: Jacob F
authors.initials: JF
authors.lastname: Degner
authors.forename: Roger
authors.initials: R
authors.lastname: Pique-Regi
authors.forename: Athma A
authors.initials: AA
authors.lastname: Pai
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.forename: Matthew
authors.initials: M
authors.lastname: Stephens
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
mesh_terms: D001499:Bayes Theorem; D002460:Cell Line; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015894:Genome, Human; D005838:Genotype; D060148:HapMap Project; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D003850:Deoxyribonuclease I