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IJE Advance Access published online on March 15, 2006
International Journal of Epidemiology, doi:10.1093/ije/dyl001
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2006; all rights reserved.
Accepted May 31, 2005

Point-Counterpoint

Dissecting complex disease: the quest for the Philosopher's Stone?

Anne V Buchanan 1, Kenneth M Weiss 2 *, and Stephanie M Fullerton 3

1 Department of Anthropology, Penn State University, University Park, PA 16802, USA
2 Department of Anthropology, Penn State University, University Park, PA 16802, USA; Department of Biology, Penn State University, University Park, PA 16802, USA
3 Department of Medical History and Ethics, University of Washington School of Medicine, Seattle, WA 98195, USA

* To whom correspondence should be addressed.
Kenneth M Weiss, E-mail: KenWeiss{at}psu.edu


  Abstract

Is the search for the causes of complex disease akin to the alchemist's vain quest for the Philosopher's Stone? Complex chronic diseases have tremendous public health impact in the industrialized world. Much effort has been expended on research into their causes, with the aim of predicting who will be affected or preventing effects before they arise, but progress has been halting at best. In this paper, we discuss possible reasons including the use of models and methods that fit point-source and Mendelian diseases but may not be as appropriate for complex diseases, reliance on causal criteria that may not be as relevant as they are for communicable diseases, and the biology of complex disease itself. Finally, we ask whether most complex diseases are even good candidates for the kind of prediction and prevention that we have come to expect based on experience with infectious and Mendelian disease.

Keywords: Complex disease; causation; Bayesian probability; epidemiology; human genetics.
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