Heritability and tissue specificity of expression quantitative trait loci

Petretto, E. et al. (2006) Heritability and tissue specificity of expression quantitative trait loci. PLoS Genetics, 2(10), e172. (doi: 10.1371/journal.pgen.0020172)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dickens, Dr Nicholas
• Authors: 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.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7404
• Copyright Holders: Copyright © 2006 The Authors
• First Published: First published in PLoS Genetics 2(10):e172
• Publisher Policy: Reproduced under a Creative Commons License