Heritability of gene expression in human cell lines

Phenotypic variation is shaped by both genetic and non-genetic factors. In analyzing the genetic basis of any trait, one of the initial tasks is to assess its heritability, which measures how much of the observed variation in the population can be explained by inherited factors. While the heritability of many human traits and diseases has been estimated, the extent of genetic influence of gene expression is still not known. We used cDNA microarrays and RT-PCR to compare transcript levels in lymphoblastoid cell lines from 24 human twin pairs, including 14 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The average correlation of gene expression is higher among the MZ twins than among the DZ twins. The heritability estimate, averaged over ~20,000 genes, is significantly above zero. This result confirms the existence of widespread genetic influences of gene expression in humans, suggesting that transcript level is a quantitative phenotype suitable for genome-wide genetic analysis. Furthermore, genes whose expression levels are strongly influenced by inherited factors are likely to contain sequence variants that affect rates of transcription or RNA stability--this study thus directly facilitates the discovery of functional polymorphisms in regulatory regions of genes.