Heritability and tissue specificity of expression quantitative trait loci

被引:156
作者
Petretto, Enrico [1 ]
Mangion, Jonathan
Dickens, Nicholas J.
Cook, Stuart A.
Kumaran, Mande K.
Lu, Han
Fischer, Judith
Maatz, Henrike
Kren, Vladimir
Pravenec, Michal
Hubner, Norbert
Aitman, Timothy J.
机构
[1] Imperial Coll, Fac Med, MRC, Ctr Clin Sci, London, England
[2] Max Delbruck Ctr Mol Med, Berlin, Germany
[3] Acad Sci Czech Republ, Inst Physiol, Prague, Czech Republic
[4] Ctr Appl Genom, Prague, Czech Republic
[5] Charles Univ Prague, Inst Biol & Med Genet, Prague, Czech Republic
来源
PLOS GENETICS | 2006年 / 2卷 / 10期
基金
英国惠康基金; 英国医学研究理事会;
关键词
D O I
10.1371/journal.pgen.0020172
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:1625 / 1633
页数:9
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