Replication validity of genetic association studies (original) (raw)

Nature Genetics volume 29, pages 306–309 (2001)Cite this article

Abstract

The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale1,2. Meta-analysis provides a quantitative approach for combining the results of various studies on the same topic, and for estimating and explaining their diversity3,4. Here, we have evaluated by meta-analysis 370 studies addressing 36 genetic associations for various outcomes of disease. We show that significant between-study heterogeneity (diversity) is frequent, and that the results of the first study correlate only modestly with subsequent research on the same association. The first study often suggests a stronger genetic effect than is found by subsequent studies. Both bias and genuine population diversity might explain why early association studies tend to overestimate the disease protection or predisposition conferred by a genetic polymorphism. We conclude that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.

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Acknowledgements

This work was supported in part by a grant from the General Secretariat for Research and Technology, Greece, funded through the European Union.

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Authors and Affiliations

  1. Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit and Clinical Trials and Evidence-Based Medicine Unit, University of Ioannina School of Medicine, Ioannina, 45110, Greece
    John P.A. Ioannidis, Evangelia E. Ntzani, Thomas A. Trikalinos & Despina G. Contopoulos-Ioannidis
  2. Ioannina Biomedical Research Institute, Ioannina, 45110, Greece
    John P.A. Ioannidis
  3. Department of Medicine, Tufts University School of Medicine, Boston, 02111, Massachusetts, USA
    John P.A. Ioannidis
  4. Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington DC, 20010, USA
    Despina G. Contopoulos-Ioannidis

Authors

  1. John P.A. Ioannidis
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  2. Evangelia E. Ntzani
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  3. Thomas A. Trikalinos
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  4. Despina G. Contopoulos-Ioannidis
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Correspondence toJohn P.A. Ioannidis.

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Ioannidis, J., Ntzani, E., Trikalinos, T. et al. Replication validity of genetic association studies.Nat Genet 29, 306–309 (2001). https://doi.org/10.1038/ng749

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