Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

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

For all author emails, please log on.

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

Published: 12 January 2011

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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 http://sites.google.com/site/kenkompass/ webcite.