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Dissecting the regulatory architecture of gene expression QTLs.

Publication ,  Journal Article
Gaffney, DJ; Veyrieras, J-B; Degner, JF; Pique-Regi, R; Pai, AA; Crawford, GE; Stephens, M; Gilad, Y; Pritchard, JK
Published in: Genome Biol
January 31, 2012

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.

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Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

January 31, 2012

Volume

13

Issue

1

Start / End Page

R7

Location

England

Related Subject Headings

  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Quantitative Trait Loci
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Humans
  • HapMap Project
  • Genotype
  • Genome, Human
  • Gene Expression
 

Citation

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Gaffney, D. J., Veyrieras, J.-B., Degner, J. F., Pique-Regi, R., Pai, A. A., Crawford, G. E., … Pritchard, J. K. (2012). Dissecting the regulatory architecture of gene expression QTLs. Genome Biol, 13(1), R7. https://doi.org/10.1186/gb-2012-13-1-r7
Gaffney, Daniel J., Jean-Baptiste Veyrieras, Jacob F. Degner, Roger Pique-Regi, Athma A. Pai, Gregory E. Crawford, Matthew Stephens, Yoav Gilad, and Jonathan K. Pritchard. “Dissecting the regulatory architecture of gene expression QTLs.Genome Biol 13, no. 1 (January 31, 2012): R7. https://doi.org/10.1186/gb-2012-13-1-r7.
Gaffney DJ, Veyrieras J-B, Degner JF, Pique-Regi R, Pai AA, Crawford GE, et al. Dissecting the regulatory architecture of gene expression QTLs. Genome Biol. 2012 Jan 31;13(1):R7.
Gaffney, Daniel J., et al. “Dissecting the regulatory architecture of gene expression QTLs.Genome Biol, vol. 13, no. 1, Jan. 2012, p. R7. Pubmed, doi:10.1186/gb-2012-13-1-r7.
Gaffney DJ, Veyrieras J-B, Degner JF, Pique-Regi R, Pai AA, Crawford GE, Stephens M, Gilad Y, Pritchard JK. Dissecting the regulatory architecture of gene expression QTLs. Genome Biol. 2012 Jan 31;13(1):R7.

Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

January 31, 2012

Volume

13

Issue

1

Start / End Page

R7

Location

England

Related Subject Headings

  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Quantitative Trait Loci
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Humans
  • HapMap Project
  • Genotype
  • Genome, Human
  • Gene Expression