Email updates

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

Open Access Highly Accessed Methodology article

A statistical approach to finding overlooked genetic associations

Andrew K Rider134, Geoffrey Siwo23, Nitesh V Chawla14, Michael Ferdig234 and Scott J Emrich13*

Author Affiliations

1 Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana, USA

2 Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA

3 Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA

4 Interdisciplinary Center for Network Science and Applications, University of Notre Dame, Notre Dame, Indiana, USA

For all author emails, please log on.

BMC Bioinformatics 2010, 11:526  doi:10.1186/1471-2105-11-526

Published: 21 October 2010

Abstract

Background

Complexity and noise in expression quantitative trait loci (eQTL) studies make it difficult to distinguish potential regulatory relationships among the many interactions. The predominant method of identifying eQTLs finds associations that are significant at a genome-wide level. The vast number of statistical tests carried out on these data make false negatives very likely. Corrections for multiple testing error render genome-wide eQTL techniques unable to detect modest regulatory effects.

We propose an alternative method to identify eQTLs that builds on traditional approaches. In contrast to genome-wide techniques, our method determines the significance of an association between an expression trait and a locus with respect to the set of all associations to the expression trait. The use of this specific information facilitates identification of expression traits that have an expression profile that is characterized by a single exceptional association to a locus.

Our approach identifies expression traits that have exceptional associations regardless of the genome-wide significance of those associations. This property facilitates the identification of possible false negatives for genome-wide significance. Further, our approach has the property of prioritizing expression traits that are affected by few strong associations. Expression traits identified by this method may warrant additional study because their expression level may be affected by targeting genes near a single locus.

Results

We demonstrate our method by identifying eQTL hotspots in Plasmodium falciparum (malaria) and Saccharomyces cerevisiae (yeast). We demonstrate the prioritization of traits with few strong genetic effects through Gene Ontology (GO) analysis of Yeast. Our results are strongly consistent with results gathered using genome-wide methods and identify additional hotspots and eQTLs.

Conclusions

New eQTLs and hotspots found with this method may represent regions of the genome or biological processes that are controlled through few relatively strong genetic interactions. These points of interest warrant experimental investigation.