Open Access Research article

Synthesis of 53 tissue and cell line expression QTL datasets reveals master eQTLs

Xiaoling Zhang1, Hinco J Gierman2, Daniel Levy1, Andrew Plump3, Radu Dobrin4, Harald HH Goring5, Joanne E Curran5, Matthew P Johnson5, John Blangero5, Stuart K Kim2, Christopher J O’Donnell16, Valur Emilsson7 and Andrew D Johnson1*

Author Affiliations

1 Division of Intramural Research, National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, The Framingham Heart Study, 73 Mt. Wayte Ave., Suite #2, Framingham, MA, USA

2 Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA

3 Sanofi Aventis Pharmaceuticals, Bridgewater, NJ 08807, USA

4 Johnson & Johnson Pharmaceutical Research and Development, Radnor, PA 19477, USA

5 Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227, USA

6 Division of Cardiology, Massachusetts General Hospital, Boston, MA 02114, USA

7 Icelandic Heart Association, Kopavogur, Iceland

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BMC Genomics 2014, 15:532  doi:10.1186/1471-2164-15-532

Published: 27 June 2014



Gene expression genetic studies in human tissues and cells identify cis- and trans-acting expression quantitative trait loci (eQTLs). These eQTLs provide insights into regulatory mechanisms underlying disease risk. However, few studies systematically characterized eQTL results across cell and tissues types. We synthesized eQTL results from >50 datasets, including new primary data from human brain, peripheral plaque and kidney samples, in order to discover features of human eQTLs.


We find a substantial number of robust cis-eQTLs and far fewer trans-eQTLs consistent across tissues. Analysis of 45 full human GWAS scans indicates eQTLs are enriched overall, and above nSNPs, among positive statistical signals in genetic mapping studies, and account for a significant fraction of the strongest human trait effects. Expression QTLs are enriched for gene centricity, higher population allele frequencies, in housekeeping genes, and for coincidence with regulatory features, though there is little evidence of 5′ or 3′ positional bias. Several regulatory categories are not enriched including microRNAs and their predicted binding sites and long, intergenic non-coding RNAs. Among the most tissue-ubiquitous cis-eQTLs, there is enrichment for genes involved in xenobiotic metabolism and mitochondrial function, suggesting these eQTLs may have adaptive origins. Several strong eQTLs (CDK5RAP2, NBPFs) coincide with regions of reported human lineage selection. The intersection of new kidney and plaque eQTLs with related GWAS suggest possible gene prioritization. For example, butyrophilins are now linked to arterial pathogenesis via multiple genetic and expression studies. Expression QTL and GWAS results are made available as a community resource through the NHLBI GRASP database [ webcite].


Expression QTLs inform the interpretation of human trait variability, and may account for a greater fraction of phenotypic variability than protein-coding variants. The synthesis of available tissue eQTL data highlights many strong cis-eQTLs that may have important biologic roles and could serve as positive controls in future studies. Our results indicate some strong tissue-ubiquitous eQTLs may have adaptive origins in humans. Efforts to expand the genetic, splicing and tissue coverage of known eQTLs will provide further insights into human gene regulation.

eQTL; RNA; Gene expression; Genomics; Transcriptome; GWAS; Genome-wide; Tissue; Cis; Trans