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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. and Mangion, J. and Dickens, N.J. and Cook, S.A. and Kumaran, M.K. and Lu, H. and Fischer, J. and Maatz, H. and Kren, V. and Pravenec, M. and Huebner, 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
ISSN:1553-7390
Publisher:Public Library of Science (U.S.A.)
Volume:2
Number:10
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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