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Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer
Kenneth S Kompass1, John S Witte
1Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California, San Francisco, USA.
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/.
