How replicable are mRNA expression QTL?

Applying quantitative trait analysis methods to genome-wide microarray-derived mRNA expression phenotypes in segregating populations is a valuable tool in the attempt to link high-level traits to their molecular causes. The massive multiple-testing issues involved in analyzing these data make the co...

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Bibliographic Details
Published in:Mammalian genome 2006-06, Vol.17 (6), p.643-656
Main Authors: Peirce, Jeremy L, Li, Hongqiang, Wang, Jintao, Manly, Kenneth F, Hitzemann, Robert J, Belknap, John K, Rosen, Glenn D, Goodwin, Shirlean, Sutter, Thomas R, Williams, Robert W, Lu, Lu
Format: Article
Language:English
Subjects:
Abundance
Animals
Chromosome Mapping
Forebrain
Gene expression
Gene Expression Profiling
Genetic Variation
Genomes
Genomics
Genotypes
Inbreeding
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Neostriatum
Phenotypes
Quantitative Trait Loci
Reproducibility of Results
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
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Summary:Applying quantitative trait analysis methods to genome-wide microarray-derived mRNA expression phenotypes in segregating populations is a valuable tool in the attempt to link high-level traits to their molecular causes. The massive multiple-testing issues involved in analyzing these data make the correct level of confidence to place in mRNA abundance quantitative trait loci (QTL) a difficult problem. We use a unique resource to directly test mRNA abundance QTL replicability in mice: paired recombinant inbred (RI) and F(2) data sets derived from C57BL/6J (B6) and DBA/2J (D2) inbred strains and phenotyped using the same Affymetrix arrays. We have one forebrain and one striatum data set pair. We describe QTL replication at varying stringencies in these data. For instance, 78% of mRNA expression QTL (eQTL) with genome-wide adjusted p < or = 0.0001 in RI data replicate at a genome-wide adjusted p < 0.05 or better. Replicated QTL are disproportionately putatively cis-acting, and approximately 75% have higher apparent expression levels associated with B6 genotypes, which may be partly due to probe set generation using B6 sequence. Finally, we note that while trans-acting QTL do not replicate well between data sets in general, at least one cluster of trans-acting QTL on distal Chr 1 is notably preserved between data sets.
ISSN:0938-8990
1432-1777
DOI:10.1007/s00335-005-0187-8