title: Sequence polymorphisms cause many false cis eQTLs.
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 cis-acting factors changing mRNA levels. Instead they indicate hybridization differences caused by sequence polymorphisms in the mRNA region 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 detected and eliminated with this approach.
authors.affiliation: Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, Netherlands.
authors.forename: Rudi
authors.initials: R
authors.lastname: Alberts
authors.forename: Peter
authors.initials: P
authors.lastname: Terpstra
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Rainer
authors.initials: R
authors.lastname: Breitling
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Nap
authors.forename: Ritsert C
authors.initials: RC
authors.lastname: Jansen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods / Q000639:trends; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D012333:RNA, Messenger