Open Access Research article

Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer

Kenneth S Kompass and John S Witte*

Author Affiliations

Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA

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BMC Medical Genomics 2011, 4:6  doi:10.1186/1755-8794-4-6

Published: 12 January 2011



Expression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging.


We describe a method to identify the trans-acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed co-regulatory expression quantitative trait locus (creQTL) mapping-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping.


Applying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNβ-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNβ-induced genes and the DNA damage response.


Because of the importance of IFNβ in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at webcite.