Common genetic variants account for differences in gene expression among ethnic groups

Abstract

Variation in DNA sequence contributes to individual differences in quantitative traits, but in humans the specific sequence variants are known for very few traits. We characterized variation in gene expression in cells from individuals belonging to three major population groups. This quantitative phenotype differs significantly between European-derived and Asian-derived populations for 1,097 of 4,197 genes tested. For the phenotypes with the strongest evidence of cis determinants, most of the variation is due to allele frequency differences at cis-linked regulators. The results show that specific genetic variation among populations contributes appreciably to differences in gene expression phenotypes. Populations differ in prevalence of many complex genetic diseases, such as diabetes and cardiovascular disease. As some of these are probably influenced by the level of gene expression, our results suggest that allele frequency differences at regulatory polymorphisms also account for some population differences in prevalence of complex diseases.

Figure 1

Gene expression in CHB+JPT (open circles) and CEU (filled circles) for eight genes that differ in mean expression level between the populations (N = 82 for CHB+JPT, and N = 60 for CEU). Additional information is found in Table 1.

Figure 2

Results of cluster analysis. The 166 individuals are represented by columns, and the 1,097 genes of the main analysis are represented by rows. For each gene, expression level for each individual is indicated by color; intensity of red is proportional to degree of expression above the mean, and intensity of green is proportional to degree of expression below the mean. The analysis grouped the individuals into two main distinguishable groups (see enlarged tree diagram at right). One group consists of 59 CEU samples, and the other consists of the 82 CHB+JPT samples, the 24 CHLA samples and 1 CEU sample.

Figure 3

The population difference in expression of POMZP3 is accounted for by the allele frequency difference at the very closely linked SNP rs2005354. The left panel shows the distribution of expression level in the same format as in Figure 1. The right panel shows the expression level separately for individuals with each genotype of the SNP.