Letter | Published:

'Racial' differences in genetic effects for complex diseases

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



'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.

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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


  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


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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

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