Genome-wide co-expression analysis in multiple tissues

Ian C Grieve, Nicholas J Dickens, Michal Pravenec, Vladimir Kren, Norbert Hubner, Stuart A Cook, Timothy J Aitman, Enrico Petretto, Jonathan Mangion

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies.

Original languageEnglish
Pages (from-to)e4033
JournalPLoS ONE
Volume3
Issue number12
DOIs
Publication statusPublished - 29 Dec 2008

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Gene Expression
  • Gene Expression Regulation
  • Genes, Regulator
  • Genetic Linkage
  • Genome
  • Genotype
  • Microsatellite Repeats
  • Models, Genetic
  • Models, Theoretical
  • Multigene Family
  • Quantitative Trait Loci
  • Rats
  • Tissue Distribution

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