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Public Library of Science, PLoS ONE, 7(2), p. e622, 2007

DOI: 10.1371/journal.pone.0000622

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Sequence Polymorphisms Cause Many False cis eQTLs

Journal article published in 2007 by Rudi Alberts, Peter Terpstra, Yang Li, Rainer Breitling ORCID, Jan-Peter Nap, Ritsert C. Jansen
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Many investigations have reported the successful mapping of quantitative trait loci (QTLs) for gene expression phenotypes (eQtLs), Local eQTLs, where expression phenotypes map to the genes themselves, are of especially great interest, because they are direct candidates for previously mapped physiological QTLs. Here we show that many mapped local eQTLs in genetical genomics experiments do not reflect actual expression differences caused by sequence polymorphisms in cisacting factor schanging mRNA levels. Instead they indicate hybridization differences caused by sequence polymorphisms in the mRNA legion that is targeted by the microarray probes. Many such polymorphisms can be detected by a sensitive and novel statistical approach that takes the individual probe signals into account. Applying this approach to recent mouse and human eQTL data, we demonstrate that indeed many local eQTLs are falsely reported as "cis-acting" or "cis" and can be successfully delected and eliminated with this approach. ?? 2007 Alberts et al.