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Bioinformatics Advance Access originally published online on July 17, 2008
Bioinformatics 2008 24(18):2015-2022; doi:10.1093/bioinformatics/btn373
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Considering dependence among genes and markers for false discovery control in eQTL mapping

Liang Chen 1,*, Tiejun Tong 2 and Hongyu Zhao 3,4,*

1Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 2Department of Applied Mathematics, University of Colorado, Boulder, CO, 3Department of Epidemiology and Public Health and 4Department of Genetics, Yale University, New Haven, CT, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Multiple comparison adjustment is a significant and challenging statistical issue in large-scale biological studies. In previous studies, dependence among genes is largely ignored. However, such dependence may be strong for some genomic-scale studies such as genetical genomics [also called expression quantitative trait loci (eQTL) mapping] in which thousands of genes are treated as quantitative traits and mapped to different genetical markers. Besides the dependence among markers, the dependence among the expression levels of genes can also have a significant impact on data analysis and interpretation.

Results: In this article, we propose to consider both the mean as well as the variance of false discovery number for multiple comparison adjustment to handle dependence among hypotheses. This is achieved by developing a variance estimator for false discovery number, and using the upper bound of false discovery proportion (uFDP) for false discovery control. More importantly, we introduce a weighted version of uFDP (wuFDP) control to improve the statistical power of eQTL identification. In addition, the wuFDP approach can better control false positives than false discovery rate (FDR) and uFDP approaches when markers are in linkage disequilibrium. The relative performance of uFDP control and wuFDP control is illustrated through simulation studies and real data analysis.

Contacts: liang.chen{at}usc.edu; hongyu.zhao{at}yale.edu

Supplementary information: Supplementary figures, tables and appendices are available at Bioinformatics online.

Associate Editor: Joaquin Dopazo

Received on January 15, 2008; revised on July 4, 2008; accepted on July 15, 2008

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