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American Journal of Epidemiology Advance Access originally published online on December 13, 2008
American Journal of Epidemiology 2009 169(4):497-504; doi:10.1093/aje/kwn339
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

PRACTICE OF EPIDEMIOLOGY

Detecting Gene-Environment Interactions Using a Combined Case-Only and Case-Control Approach

Dalin Li and David V. Conti

Correspondence to Dr. David V. Conti, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, ZNI 445, MC 2821, Los Angeles, CA 90089 (e-mail: dconti{at}usc.edu).

Received for publication May 22, 2008. Accepted for publication September 24, 2008.

The conventional method of detecting gene-environment interactions, the case-control analysis, suffers from low statistical power. In contrast, the case-only analysis/design can be powerful in certain scenarios, although violation of the assumption of independence between the genetic and environmental factors can greatly bias the results. As an alternative, Bayes model averaging may be used to combine the case-control and case-only analyses. This approach first frames the case-control and case-only analyses as variations of a log-linear model. The weighting between these 2 models is then a function of the data and prior beliefs on the independence of the 2 potentially interacting factors. In this paper, the authors demonstrate via simulations that when there is no prior information on the independence of the genetic and environmental factors, this approach tends to be more powerful than the case-control analysis. Additionally, when the genetic and environmental factors are not independent in the population, bias is substantially reduced, with a corresponding reduction in type I error in comparison with the case-only analysis. Increased power or increased robustness to violations of the independence assumption may be obtained with more appropriate prior specification. The authors use an example data analysis to demonstrate the advantages of this approach.

Bayesian estimation; Bayesian model; case-control studies; epidemiologic methods; interaction

Abbreviations: BMA, Bayes model averaging; FREQ, frequenin homolog (Drosophila); MAOA, monoamine oxidase A; MSE, mean squared error; SNP, single nucleotide polymorphism; VNTR, variable number of tandem repeats


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