Article

Single-Tissue and Cross-Tissue Heritability of Gene Expression Via Identity-by-Descent in Related or Unrelated Individuals

Georgia Institute of Technology, United States of America
PLoS Genetics (Impact Factor: 8.17). 02/2011; 7(2):e1001317. DOI: 10.1371/journal.pgen.1001317
Source: PubMed

ABSTRACT Author Summary
An important goal in biology is to understand how genotype affects gene expression. Because gene expression varies across tissues, the relationship between genotype and gene expression may be tissue-specific. In this study, we used heritability approaches to study the regulation of gene expression in two tissue types, blood and adipose tissue, as well as the regulation of gene expression that is shared across these tissues. Heritability can be partitioned into cis and trans effects by assessing identity-by-descent (IBD) at the genomic location close to the expressed gene or genome-wide, respectively, and applying variance-components methods to partition the heritability of each gene. We estimated the proportion of gene expression heritability explained by cis regulation as 37% in blood and 24% in adipose tissue. Notably, the heritability shared across tissue types was primarily due to cis regulation. Thus, the relative contribution of cis versus trans regulation is expected to increase with the number of cell types present in the tissue being assayed, just as observed in our study and in a comparison to previous work on lymphoblastoid cell lines (LCL). We specifically ruled out a substantial contribution of transgenerational epigenetic inheritance to heritability of gene expression in these cohorts by repeating our heritability analyses using segments shared IBD in distantly related Icelanders.

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    • "Genome-wide expression quantitative trait locus (eQTL) mapping has been widely used to identify common genetic variants regulating gene expression (Myers et al. 2007; Schadt et al. 2008; Stranger et al. 2005, 2007; Zeller et al. 2010). Although numerous studies (Myers et al. 2007; Schadt et al. 2008; Stranger et al. 2005, 2007; Westra et al. 2013; Zeller et al. 2010) have revealed tens of thousands of cis and trans eQTLs, many cis and trans eQTLs remain unrecognized due to sample size limitations and tissue specificity (Grundberg et al. 2012; Price et al. 2011). "
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    • "A median heritability of 0.35 for transcript expression has been reported for human lymphoblastoid cell lines, though this estimate may be upwardly biased given that heritability was estimated only for differentially expressed transcripts (Monks et al. 2004). Other human studies show that average transcript heritability differs across tissues: 0.37 in blood and only 0.24 in adipose (Price et al. 2011)—95% quantiles of nonzero estimates from this study overlap (blood = 0.018–0.497; adipose = 0.042–0.539), "
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    • "Multivariate linear mixed models (mvLMMs) [2] have been applied to many areas of genetics, including, for example, estimating the cross-tissue heritability of gene expression [3], assessing the pleiotropy and genetic correlation between complex phenotypes [1] [4] [5] [6], detecting quantitative * xz7@uchicago.edu † mstephens@uchicago.edu "
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