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Heritability and tissue specificity of expression quantitative trait loci

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Item Type:Article
Title:Heritability and tissue specificity of expression quantitative trait loci
Creators Name:Petretto, E., Mangion, J., Dickens, N.J., Cook, S.A., Kumaran, M.K., Lu, H., Fischer, J., Maatz, H., Kren, V., Pravenec, M., Hubner, N. and Aitman, T.J.
Abstract:Variation in gene expression is heritable and has been mapped to the genome in humans and model organisms as expression quantitative trait loci (eQTLs). We applied integrated genome-wide expression profiling and linkage analysis to the regulation of gene expression in fat, kidney, adrenal, and heart tissues using the BXH/HXB panel of rat recombinant inbred strains. Here, we report the influence of heritability and allelic effect of the quantitative trait locus on detection of cis- and trans-acting eQTLs and discuss how these factors operate in a tissue-specific context. We identified several hundred major eQTLs in each tissue and found that cis-acting eQTLs are highly heritable and easier to detect than trans-eQTLs. The proportion of heritable expression traits was similar in all tissues; however, heritability alone was not a reliable predictor of whether an eQTL will be detected. We empirically show how the use of heritability as a filter reduces the ability to discover trans-eQTLs, particularly for eQTLs with small effects. Only 3% of cis- and trans-eQTLs exhibited large allelic effects, explaining more than 40% of the phenotypic variance, suggestive of a highly polygenic control of gene expression. Power calculations indicated that, across tissues, minor differences in genetic effects are expected to have a significant impact on detection of trans-eQTLs. Trans-eQTLs generally show smaller effects than cis-eQTLs and have a higher false discovery rate, particularly in more heterogeneous tissues, suggesting that small biological variability, likely relating to tissue composition, may influence detection of trans-eQTLs in this system. We delineate the effects of genetic architecture on variation in gene expression and show the sensitivity of this experimental design to tissue sampling variability in large-scale eQTL studies.
Keywords:Alleles, Gene Expression Regulation, Genome, Organ Specificity, Quantitative Trait Loci, Heritable Quantitative Trait, Messenger RNA, Animals, Rats
Source:PLoS Genetics
Publisher:Public Library of Science
Page Range:1625-1633
Date:20 October 2006
Official Publication:https://doi.org/10.1371/journal.pgen.0020172
PubMed:View item in PubMed

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