Common genetic variants account for differences in gene expression among ethnic groups (original) (raw)

Nature Genetics volume 39, pages 226–231 (2007)Cite this article

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.

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References

  1. Schadt, E.E. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003).
    Article CAS PubMed Google Scholar
  2. Cheung, V.G. et al. Natural variation in human gene expression assessed in lymphoblastoid cells. Nat. Genet. 33, 422–425 (2003).
    Article CAS PubMed Google Scholar
  3. Cheung, V.G. et al. Mapping determinants of human gene expression by regional and genome-wide association. Nature 437, 1365–1369 (2005).
    Article CAS PubMed PubMed Central Google Scholar
  4. Morley, M. et al. Genetic analysis of genome-wide variation in human gene expression. Nature 430, 743–747 (2004).
    Article CAS PubMed PubMed Central Google Scholar
  5. Stranger, B.E. et al. Genome-wide associations of gene expression variation in humans. PLoS Genet. 1, e78 (2005).
    Article PubMed PubMed Central Google Scholar
  6. Monks, S.A. et al. Genetic inheritance of gene expression in human cell lines. Am. J. Hum. Genet. 75, 1094–1105 (2004).
    Article CAS PubMed PubMed Central Google Scholar
  7. Yan, H., Yuan, W., Velculescu, V.E., Vogelstein, B. & Kinzler, K.W. Allelic variation in human gene expression. Science 297, 1143 (2002).
    Article CAS PubMed Google Scholar
  8. Pastinen, T. et al. A survey of genetic and epigenetic variation affecting human gene expression. Physiol. Genomics 16, 184–193 (2004).
    Article CAS PubMed Google Scholar
  9. Tsui, L.C. Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium. Hum. Mutat. 1, 197–203 (1992).
    Article CAS PubMed Google Scholar
  10. Paw, B.H., Tieu, P.T., Kaback, M.M., Lim, J. & Neufeld, E.F. Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program. Am. J. Hum. Genet. 47, 698–705 (1990).
    CAS PubMed PubMed Central Google Scholar
  11. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
  12. Westfall, P.H. & Young, S.S. Resampling-Based Multiple Testing (John Wiley & Sons, New York, 1992).
  13. Wilson, W., III . et al. Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 84, 707–714 (2004).
    Article CAS PubMed Google Scholar
  14. McCarroll, S.A. et al. Common deletion polymorphisms in the human genome. Nat. Genet. 38, 86–92 (2006).
    Article CAS PubMed Google Scholar
  15. Hinds, D.A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).
    Article CAS PubMed Google Scholar
  16. Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14863–14868 (1998).
    Article CAS PubMed PubMed Central Google Scholar
  17. Osada, N., Kohn, M.H. & Wu, C.I. Genomic inferences of the cis-regulatory nucleotide polymorphisms underlying gene expression differences between Drosophila melanogaster mating races. Mol. Biol. Evol. 23, 1585–1591 (2006).
    Article CAS PubMed Google Scholar
  18. McEvoy, B., Beleza, S. & Shriver, M.D. The genetic architecture of normal variation in human pigmentation: An evolutionary perspective and model. Hum. Mol. Genet. 15, R176–R181 (2006).
    Article CAS PubMed Google Scholar
  19. Lamason, R.L. et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310, 1782–1786 (2005).
    Article CAS PubMed Google Scholar
  20. Knight, J.C. Regulatory polymorphisms underlying complex disease traits. J. Mol. Med. 83, 97–109 (2005).
    Article CAS PubMed Google Scholar

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Acknowledgements

We thank T. Weber for carrying out the microarray hybridizations, V. Mancuso for processing samples and data analysis and H. H. Kazazian and K. Ewens for comments on the manuscript. This work was supported by US National Institutes of Health grants (to R.S.S, V.G.C) and by the W.W. Smith Chair (V.G.C.).

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Authors and Affiliations

  1. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Richard S Spielman & Vivian G Cheung
  2. Department of Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Laurel A Bastone
  3. The Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA
    Joshua T Burdick, Michael Morley & Vivian G Cheung
  4. Department of Biology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
    Warren J Ewens
  5. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Vivian G Cheung

Authors

  1. Richard S Spielman
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  2. Laurel A Bastone
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  3. Joshua T Burdick
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  4. Michael Morley
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  5. Warren J Ewens
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  6. Vivian G Cheung
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Corresponding authors

Correspondence toRichard S Spielman or Vivian G Cheung.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Genes whose expression differs significantly between CEU and CHB+JPT samples. (PDF 89 kb)

Supplementary Table 2

Four genes with evidence for differences in mean expression between CEU and CHB+JPT due to different regulatory mechanisms. (PDF 67 kb)

Supplementary Table 3

Four genes with evidence for differences in mean expression between CEU and CHB+JPT due to different regulatory mechanisms. (PDF 69 kb)

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Spielman, R., Bastone, L., Burdick, J. et al. Common genetic variants account for differences in gene expression among ethnic groups.Nat Genet 39, 226–231 (2007). https://doi.org/10.1038/ng1955

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