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Evaluating Disorders with a Complex Genetics Basis. The Future Roles of Meta-analysis and Systems Biology

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Abstract

Growing evidence suggests that complex gene and environment interactions underlie a number of diseases including chronic inflammatory diseases of the digestive system. The rapid advances in information and technology provide opportunities to discover the risks or etiology for a variety of disorders within individual patients. However, the availability of new data and new technology has outstripped the conceptual framework of simple disorders and challenges current statistical approaches. Here we address the issues surrounding study design and sample size for complex genetic traits, with special attention to meta-analysis and systems biology. We conclude that meta-analysis should play a limited role in evaluating studies of complex genetic diseases. Instead, systems biology-based approaches should be developed to integrate multiple, focused, and mechanistic association studies with the goal of assisting in the risk assessment of patients on a person-by-person basis.

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Authors and Affiliations

  1. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    David C. Whitcomb MD (PD) & Elie Aoun MD

  2. Department of Cell Biology & Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    David C. Whitcomb MD (PD)

  3. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    David C. Whitcomb MD (PD) & M. Michael Barmada PhD

  4. Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    Yoram Vodovotz PhD

  5. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    Gilles Clermont MD

  6. Department of Center for Inflammation and Regenerative Modeling, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    Yoram Vodovotz PhD & Gilles Clermont MD

  7. Department of University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    David C. Whitcomb MD (PD)

  8. GI Administration UPMC Presbyterian, Mezzanine Level 2, C Wing, 200 Lothrop Street, Pittsburgh, Pennsylvania, 15213, USA

    David C. Whitcomb MD (PD)

Authors
  1. David C. Whitcomb MD
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  2. Elie Aoun MD
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  3. Yoram Vodovotz PhD
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  4. Gilles Clermont MD
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  5. M. Michael Barmada PhD
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Corresponding author

Correspondence to David C. Whitcomb MD.

Additional information

Some of this work was presented by Professor Whitcomb in an invited lecture entitled “Polygenic Traits in Pancreatic Disorders,” at the 5th International Symposium on Inherited Diseases of the Pancreas, Graz, Austria, July 9, 2005. This work was supported in part by NIH Grants DK61451 (D.C.W.) and DK054709 (D.C.W.) and by the Wayne Fusaro Pancreatic Cancer Research Fund (D.C.W.).

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Whitcomb, D.C., Aoun, E., Vodovotz, Y. et al. Evaluating Disorders with a Complex Genetics Basis. The Future Roles of Meta-analysis and Systems Biology. Dig Dis Sci 50, 2195–2202 (2005). https://doi.org/10.1007/s10620-005-3033-7

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  • DOI: https://doi.org/10.1007/s10620-005-3033-7

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