Evaluation of Genetic Variation Contributing to Differences in Gene Expression between Populations

Wei Zhang, Shiwei Duan, Emily O. Kistner, Wasim K. Bleibel, R. Stephanie Huang, Tyson A. Clark, Tina X. Chen, Anthony C. Schweitzer, John E. Blume, Nancy J. Cox, M. Eileen Dolan

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162 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - Mar 3 2008
Externally publishedYes

Bibliographical note

Funding Information:
This Pharmacogenetics of Anticancer Agents Research (PAAR) Group study was supported by grants from the National Insitutes of Health: National Institute of General Medical Sciences (GM61393 and GM61374). We are grateful to Dr. Anna Di Rienzo, Cheryl A. Roe, and Dr. Sunita J. Shukla for helpful discussions and to Dr. Jeong-Ah Kang for maintaining cell lines. We are also grateful to Dr. Jacek Majewski of McGill University, Canada for providing us with the list of exon-array probes containing dbSNPs. T.A.C., T.X.C., A.C.S., and J.E.B. are employees of Affymetrix, Inc.


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