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E-GEOD-65907 - Dissecting the Genetics of the Human Transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci

Released on 29 June 2015, last updated on 19 August 2015
Homo sapiens
Samples (2112)
Array (1)
Protocols (5)
Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2,112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters, and enrichment of co-localised functional elements. We found eQTLs for about 85% of analysed genes, 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 MB to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might often be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels, and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. We show for strongly heritable transcripts that a considerable gap still exists between total heritability resulting from all trans-chromosomes and explained variance of all identified trans-eSNPs. In contrast, the vast majority of most cis-heritability of these genes is already explained. Dissection of co-localised functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene-expression, pathways and disease related processes. Gene expression from human blood mononuclear cells from individuals of the Leipzig LIFE Heart Study was analyzed applying Illumina HT-12 v4 Expression BeadChips. After preprocessing, 28,295 expression probes for 2,112 individuals remained for analysis. In a population-based analysis, we identified associations between DNA variants and RNA expression levels and characterized these findings.
Experiment type
transcription profiling by array 
Holger Kirsten <>, Daniel Teupser, Frank Beutner, Joachim Thiery, Knut Krohn, Markus Scholz