Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 3, 631-640, 28 February 2008
doi:10.1016/j.ajhg.2007.12.015
Article
Evaluation of Genetic Variation Contributing to Differences in Gene Expression between Populations
Wei Zhang1, 5, Shiwei Duan1, 5, Emily O. Kistner2, Wasim K. Bleibel1, R. Stephanie Huang1, Tyson A. Clark4, Tina X. Chen4, Anthony C. Schweitzer4, John E. Blume4, Nancy J. Cox1, 3 and M. Eileen Dolan1, 
, 
1 Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
2 Department of Health Studies, The University of Chicago, Chicago, IL 60637, USA
3 Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA
4 Expression Research, Affymetrix Laboratory, Affymetrix, Santa Clara, CA 95051, USA
Corresponding author5 These authors contributed equally to this work.
Abstract
Gene expression is a complex quantitative trait partially regulated by genetic variation in DNA sequence. Population differences in gene expression could contribute to some of the observed differences in susceptibility to common diseases and response to drug treatments. We characterized gene expression in the full set of HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry for 9156 transcript clusters (gene-level) evaluated with the Affymetrix GeneChip Human Exon 1.0 ST Array. Gene expression was found to differ significantly between these samples for 383 transcript clusters. Biological processes including ribosome biogenesis and antimicrobial humoral response were found to be enriched in these differential genes, suggesting their possible roles in contributing to the population differences at a higher level than that of mRNA expression and in response to environmental information. Genome-wide association studies for local or distant genetic variants that correlate with the differentially expressed genes enabled identification of significant associations with one or more single-nucleotide polymorphisms (SNPs), consistent with the hypothesis that genetic factors and not simply population identity or other characteristics (age of cell lines, length of culture, etc.) contribute to differences in gene expression in these samples. Our results provide a comprehensive view of the genes differentially expressed between populations and the enriched biological processes involved in these genes. We also provide an evaluation of the contributions of genetic variation and nongenetic factors to the population differences in gene expression.
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