Abstract
Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental) effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes) at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis) versus ancestry elsewhere in the genome (trans). Both effects are highly significant, and we estimate that 12±3% of all heritable variation in human gene expression is due to cis variants.
Highlights
Admixed populations are uniquely useful for analyzing the genetic contribution to phenotypic differences among humans
Variation in gene expression is a fundamental aspect of human phenotypic variation, and understanding how this variation is apportioned among human populations is an important aim
Admixed populations, such as African Americans, offer a solution to this problem because individuals vary in their proportion of European ancestry while the analysis of a single population minimizes nongenetic factors
Summary
Admixed populations are uniquely useful for analyzing the genetic contribution to phenotypic differences among humans. Several recent epidemiological studies in African Americans have taken advantage of this, showing that many phenotypic traits vary with the proportion of European ancestry [3,4,5] We apply this idea to analyze population differences in gene expression. Four studies analyzed lymphoblastoid cell lines from HapMap samples and reported that a large number of expressed genes exhibit significant differences in gene expression among continental populations [7,8,9,10]. Results of these studies may be affected by nongenetic factors such as differences in environment, differences in preparation of cell lines, or batch effects [2,9,11,12]. Analyses of expression differences that are correlated to ancestry within an admixed population are robust to all of these concerns
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