Letter | Published:

'Racial' differences in genetic effects for complex diseases

Nature Genetics volume 36, pages 13121318 (2004) | Download Citation

Subjects

Abstract

'Racial' differences are frequently debated in clinical, epidemiological and molecular research and beyond1,2. In particular, there is considerable controversy regarding the existence and importance of 'racial' differences in genetic effects for complex diseases3,4,5,6 influenced by a large number of genes7. An important question is whether ancestry influences the impact of each gene variant on the disease risk. Here, we addressed this question by examining the genetic effects for 43 validated gene-disease associations across 697 study populations of various descents. The frequencies of the genetic marker of interest in the control populations often (58%) showed large heterogeneity (statistical variability) between 'races'. Conversely, we saw large heterogeneity in the genetic effects (odds ratios) between 'races' in only 14% of cases. Genetic markers for proposed gene-disease associations vary in frequency across populations, but their biological impact on the risk for common diseases may usually be consistent across traditional 'racial' boundaries.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , & Race and genomics. N. Engl. J. Med. 348, 1166–1170 (2003).

  2. 2.

    et al. The importance of race and ethnic background in biomedical research and clinical practice. N. Engl. J. Med. 348, 1170–1175 (2003).

  3. 3.

    The International HapMap Consortium. The International HapMap Project. Nature 426, 789–796 (2003).

  4. 4.

    & Point: population stratification: a problem for case-control studies of candidate-gene associations? Cancer Epidemiol. Biomarkers Prev. 11, 505–512 (2002).

  5. 5.

    & Commentary: considerations for use of racial/ethnic classification in etiologic research. Am. J. Epidemiol. 154, 291–298 (2001).

  6. 6.

    , & Counterpoint: bias from population stratification is not a major threat to the validity of conclusions from epidemiological studies of common polymorphisms and cancer. Cancer Epidemiol. Biomarkers Prev. 11, 513–520 (2002).

  7. 7.

    & Genetic dissection of complex traits. Science 265, 2037–2048 (1994).

  8. 8.

    et al. Genetic structure of human populations. Science 298, 2381–2385 (2002).

  9. 9.

    & Human genetics. Mapping human history. Science 298, 2342–2343 (2002).

  10. 10.

    , & Race: a genetic melting-pot. Nature 424, 374 (2003).

  11. 11.

    , , & Categorization of humans in biomedical research: genes, race and disease. Genome Biol. 3, 2007 (2002).

  12. 12.

    , , & Agreement between administrative data and patients' self-reports of race/ethnicity. Am. J. Public Health 93, 1734–1739 (2003).

  13. 13.

    , , & Replication validity of genetic association studies. Nat. Genet. 29, 306–309 (2001).

  14. 14.

    , , & Genetic associations in large versus small studies: an empirical assessment. Lancet 361, 567–571 (2003).

  15. 15.

    Meta-analysis, Decision Analysis and Cost-Effectiveness Analysis (Oxford University Press, New York, 1999).

  16. 16.

    & Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539–1558 (2002).

  17. 17.

    The case for a US prospective cohort study of genes and environment. Nature 429, 475–477 (2004).

  18. 18.

    et al. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).

  19. 19.

    & The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66, 1191–1308 (1981).

  20. 20.

    & Association study designs for complex diseases. Nat. Rev. Genet. 2, 91–99 (2001).

Download references

Acknowledgements

J.P.A.I. generated the idea for this project and wrote the protocol that was further elaborated by the other two authors. E.E.N. carried out additional data extraction with help from T.A.T. These two authors carried out the statistical analyses with contribution from J.P.A.I. All authors interpreted the data and the analyses. The final draft was written by J.P.A.I. and commented on critically by the other two authors. We thank D. Contopoulos-Ioannidis for her scientific contribution to important background work for this project and A. Wu, S. Glatt, M. Preisig, A. Lalovic, R. Inzelberg and L. Le Marchand for providing additional data on their published meta-analyses. The project was supported by a PENED grant from the General Secretariat for Research and Technology, Greece and the European Commission.

Author information

Affiliations

  1. Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.

    • John P A Ioannidis
    • , Evangelia E Ntzani
    •  & Thomas A Trikalinos
  2. Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, 45110, Greece.

    • John P A Ioannidis
  3. Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

    • John P A Ioannidis
    •  & Thomas A Trikalinos

Authors

  1. Search for John P A Ioannidis in:

  2. Search for Evangelia E Ntzani in:

  3. Search for Thomas A Trikalinos in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John P A Ioannidis.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Control frequencies and effect sizes for overall-validated marker-disease associations.

  2. 2.

    Supplementary Table 1

    Included and excluded meta-analyses of gene-diseases associations.

  3. 3.

    Supplementary Table 2

    Within-race and between-race variance for control frequencies.

  4. 4.

    Supplementary Table 3

    Pair-wise comparisons for control frequencies.

  5. 5.

    Supplementary Table 4

    Within-race and between-race variance for odds ratios.

  6. 6.

    Supplementary Table 5

    Pair-wise comparisons for odds ratios.

  7. 7.

    Supplementary Note

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng1474

Further reading