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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