© 2004 by Oxford University Press
© 2004 Oxford University Press
EDITORIAL |
Betting Odds and Genetic Associations
Affiliations of authors: Department of Preventive Medicine, University of Southern California, Los Angeles, CA (DCT); Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge, U.K. (DGC)
Correspondence to: Duncan C. Thomas, PhD, Department of Preventive Medicine, University of Southern California, 1540 Alcazar St., CHP-220, Los Angeles, CA 90089-9011 (e-mail: dthomas@usc.edu)
| The first 150 words of the full text of this article appear below. |
"Multiple Comparisons? No Problem!" read the title of an editorial in an issue of Epidemiology in 1991 (1). Attitudes toward multiple comparisons have swung like a pendulum, the view quoted above representing one end of a cycle that has been reversed in recent years. Few classical risk factor epidemiology studies test more than a few hundred associations between exposures and diseases, even in an exploratory mode. In molecular epidemiology, however, the growing feasibility of testing many thousands, or even millions, of single nucleotide polymorphisms (SNPs) associations in genome-wide studies have forced even the most liberal investigators to re-examine their positions on multiple hypothesis testing (2,3). These concerns have been reinforced by the observation that an alarming proportion of reported associations between genetic variants and diseases are not replicated (4–6).
In the classical theory of multiple comparisons for
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