Genetic control of gene expression in whole blood and lymphoblastoid cell lines is largely independent

Abstract

The degree to which the level of genetic variation for gene expression is shared across multiple tissues has important implications for research investigating the role of expression on the etiology of complex human traits and diseases. In the last few years, several studies have been published reporting the extent of overlap in expression quantitative trait loci (eQTL) identified in multiple tissues or cell types. Although these studies provide important information on the regulatory control of genes across tissues, their limited power means that they can typically only explain a small proportion of genetic variation for gene expression. Here, using expression data from monozygotic twins (MZ), we investigate the genetic control of gene expression in lymphoblastoid cell lines (LCL) and whole blood (WB). We estimate the genetic correlation that represents the combined effects of all causal loci across the whole genome and is a measure of the level of common genetic control of gene expression between the two RNA sources. Our results show that, when averaged across the genome, mean levels of genetic correlation for gene expression in LCL and WB samples are close to zero. We support our results with evidence from gene expression in an independent sample of LCL, T-cells, and fibroblasts. In addition, we provide evidence that housekeeping genes, which maintain basic cellular functions, are more likely to have high genetic correlations between the RNA sources than non-housekeeping genes, implying a relationship between the transcript function and the degree to which a gene has tissue-specific genetic regulatory control.

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

“…We found no compelling evidence for a common set of highly heritable DNA methylation variants across different tissues, supporting similar findings in a study of ASM in multiple human cell lines (Shoemaker et al 2010) and recent data using gene expression as a phenotypic outcome (Powell et al 2012). This contrasts with a subset of recently described ASM events described in a single individual that appear to be shared across kidney and skeletal muscle (Gertz et al 2011).…”

Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort

“…Expression quantitative trait locus (eQTL) SNPs are more likely to associate with complex trait [10]. For example, comparison of lymphoblastoid cell lines (LCLs) and whole blood demonstrates near zero genetic correlation of gene expression; while tissue-specific expression of non-housekeeping genes is more likely [11]. Recently, we have identified SNPs in GSDMB , TSLP , IL33 , and HLA-DQB1 affect asthma via tissue-specific cis-regulation of gene expression [12].…”

Genetic and Nongenetic Variation Revealed for the Principal Components of Human Gene Expression

“…Gene expression acts as an intermediate phenotype between genotypes and complex traits and is known to act as a modifier to disease susceptibility (Nica and Dermitzakis 2008;Li et al 2012). Genetic variation underlying gene expression levels has been well established and reported within the literature, with the transcript levels for the majority of genes being heritable to some degree (Price et al 2011;Grundberg et al 2012;Powell et al 2012b).Microarray technology can simultaneously capture the expression of thousands of transcripts within an individual.However, these arrays are sensitive to environmental or experimental perturbations, for example due to different laboratory technicians and reagents (Churchill 2002;Irizarry et al 2005), microarray chip and chip position (Luo et al 2010), temperature (Scherer 2009), and even ozone levels (Thomas et al 2003). These effects can constitute a substantial proportion of variance within a data set (Leek et al 2010).…”

“…Gene expression acts as an intermediate phenotype between genotypes and complex traits and is known to act as a modifier to disease susceptibility (Nica and Dermitzakis 2008;Li et al 2012). Genetic variation underlying gene expression levels has been well established and reported within the literature, with the transcript levels for the majority of genes being heritable to some degree (Price et al 2011;Grundberg et al 2012;Powell et al 2012b).…”