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Comparing methods for mapping cis acting polymorphisms using allelic expression ratios

Teare, M.D., Pinyakorn, S., Heighway, J. and Koref, M.F.S. (2011) Comparing methods for mapping cis acting polymorphisms using allelic expression ratios. PLoS One, 6 (12). Art no. e28636. ISSN 1932-6203


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Genome wide association studies frequently reveal associations between disease susceptibility and polymorphisms outside coding regions. Such associations cannot always be explained by linkage disequilibrium with changes affecting the transcription products. This has stimulated the interest in characterising sequence variation influencing gene expression levels, in particular in changes acting in cis. Differences in transcription between the two alleles at an autosomal locus can be used to test the association between candidate polymorphisms and the modulation of gene expression in cis. This type of approach requires at least one transcribed polymorphism and one candidate polymorphism. In the past five years, different methods have been proposed to analyse such data. Here we use simulations and real data sets to compare the power of some of these methods. The results show that when it is not possible to determine the phase between the transcribed and potentially cis acting allele there is some advantage in using methods that estimate phased genotype and effect on expression simultaneously. However when the phase can be determined, simple regression models seem preferable because of their simplicity and flexibility. The simulations and the analysis of experimental data suggest that in the majority of situations, methods that assume a lognormal distribution of the allelic expression ratios are both robust to deviations from this assumption and more powerful than alternatives that do not make these assumptions.

Item Type: Article
Copyright, Publisher and Additional Information: © 2011 Teare et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Gene-Expression; Cancer; Imbalance; Ligation; Tissue; Cells
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 27 Jan 2012 13:50
Last Modified: 09 Jun 2014 10:51
Published Version: http://dx.doi.org/10.1371/journal.pone.0028636
Status: Published
Publisher: Public Library Science
Refereed: Yes
Identification Number: 10.1371/journal.pone.0028636
URI: http://eprints.whiterose.ac.uk/id/eprint/43682

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